Tianeptine as conceived by ChatGPT

Source: OpenAI ChapGPT
Date: 2023

ChatGPT on Tianeptine

Answers to prompts by webmaster DP to ChatGPT-4 April 2023

David Pearce Give an overview of tianeptine
"Tianeptine is an atypical antidepressant medication that is primarily used to treat major depressive disorder, anxiety, and other mood disorders. It was developed in the 1960s and has been marketed under various brand names, including Stablon, Coaxil, and Tatinol. Tianeptine has a unique pharmacological profile compared to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
Mechanism of Action: Tianeptine's precise mechanism of action is not fully understood, but it is known to have a modulatory effect on the glutamatergic system, specifically by acting on NMDA and AMPA receptors. This modulation is believed to contribute to its antidepressant and anxiolytic effects. Additionally, tianeptine has opioidergic activity, acting as a full agonist at the mu-opioid receptor, which may also contribute to its mood-enhancing properties.
Pharmacokinetics: Tianeptine is rapidly absorbed and has a short half-life, typically ranging from 2 to 3 hours. It is metabolized by the liver and excreted primarily in the urine. Its two active metabolites, MC5 and MC3, are also involved in its pharmacological effects.
Indications: Tianeptine is prescribed primarily for major depressive disorder but has also shown efficacy in treating anxiety, post-traumatic stress disorder (PTSD), and irritable bowel syndrome (IBS). Some research has indicated potential utility in treating other conditions, such as fibromyalgia and attention deficit disorder, but further studies are needed.
Side Effects: Tianeptine is generally well-tolerated, with a lower incidence of side effects compared to other antidepressants. Common side effects may include dizziness, dry mouth, constipation, headache, and insomnia. However, at higher doses or with misuse, tianeptine can cause euphoria and has the potential for abuse and dependence due to its opioidergic properties.
Contraindications and Drug Interactions: Tianeptine should be used with caution in individuals with a history of substance abuse or dependence, and those with liver or kidney impairment. It may also interact with other medications, such as monoamine oxidase inhibitors (MAOIs) and certain pain medications, so it is essential to consult a healthcare professional before combining tianeptine with other treatments.
Dosage: The recommended dosage of tianeptine for adults is typically 12.5 mg taken three times a day. Dosage adjustments may be necessary for individuals with specific medical conditions or those taking certain medications.
It is important to note that the effects and safety of tianeptine can vary between individuals, and it is always recommended to consult with a healthcare professional before starting, changing, or stopping any medication."
Outline the history of tianeptine
"Tianeptine is an atypical antidepressant and anxiolytic medication with a unique mechanism of action that was first synthesized in the 1960s. Here is a brief outline of its history:
Discovery and synthesis (1960s): Tianeptine was first synthesized by the French pharmaceutical company Laboratoires Servier in the 1960s as part of their research efforts to develop novel antidepressants.
Initial clinical trials (1970s-1980s): Clinical trials investigating the safety and efficacy of tianeptine for the treatment of depression began in the 1970s and continued through the 1980s. These trials demonstrated that tianeptine was effective in treating depression and had a favorable side effect profile compared to other antidepressants available at the time.
Market approval and use (late 1980s-1990s): Tianeptine was first approved for use as an antidepressant in France in 1989 under the brand name Stablon. Over the following years, it was approved and marketed in several other countries, primarily in Europe, Latin America, and Asia. Its unique mechanism of action, involving both glutamatergic and opioidergic systems, set it apart from other antidepressants, which mainly targeted the monoaminergic neurotransmitter systems.
Mechanism of action discovery (2000s): The precise mechanism of action of tianeptine remained elusive for years. In 2014, researchers discovered that tianeptine is a mu-opioid receptor (MOR) agonist and a full agonist of the delta-opioid receptor (DOR), which provided crucial insights into its antidepressant and anxiolytic effects.
Potential alternative uses and safety concerns (2010s-2020s): As researchers gained a better understanding of tianeptine's mechanism of action, interest grew in its potential for alternative uses, such as pain management and opioid withdrawal. However, concerns about its potential for abuse and dependence due to its opioidergic properties also emerged, leading to increased regulatory scrutiny and restrictions on its use in some countries.
In summary, the history of tianeptine spans from its synthesis in the 1960s to its approval as an antidepressant in the late 1980s and ongoing research into its unique mechanism of action and potential alternative uses. As our understanding of tianeptine's pharmacology and safety profile continues to evolve, its role in the treatment of depression, anxiety, and other conditions remains an area of active research and discussion."
What is the mechanism of action of tianeptine in the brain?
"Tianeptine is an atypical antidepressant and anxiolytic medication with a unique mechanism of action that distinguishes it from other classes of antidepressants. Its mechanism of action in the brain involves several neurotransmitter systems, primarily the opioidergic and glutamatergic systems.
Opioidergic system: Tianeptine acts as an agonist of the mu-opioid receptor (MOR) and delta-opioid receptor (DOR). This action is thought to contribute to its antidepressant and anxiolytic effects. Unlike traditional opioids, tianeptine has a much weaker affinity for these receptors, which reduces the risk of side effects, such as respiratory depression, typically associated with opioid drugs.
Glutamatergic system: Tianeptine modulates the glutamatergic system, particularly by enhancing the reuptake of glutamate, the major excitatory neurotransmitter in the brain. This modulation is believed to play a key role in tianeptine's neuroprotective and antidepressant effects. Tianeptine also affects the levels and function of other neurotransmitters, such as dopamine and serotonin, but to a lesser extent than its impact on the glutamatergic system.
Neuroplasticity and neuroprotection: Tianeptine has been shown to promote neuroplasticity and protect neurons from damage caused by stress and other factors. These effects may contribute to its long-term benefits in treating depression and anxiety. Tianeptine has been found to increase the expression of brain-derived neurotrophic factor (BDNF), which plays a crucial role in supporting the growth, survival, and differentiation of neurons.
Stress response modulation: Tianeptine may also modulate the stress response by affecting the hypothalamic-pituitary-adrenal (HPA) axis, which is involved in the body's response to stress. Dysregulation of the HPA axis has been implicated in the pathophysiology of depression and anxiety disorders. Tianeptine has been shown to normalize the HPA axis function in animal models of stress, which may contribute to its therapeutic effects.
In summary, the mechanism of action of tianeptine in the brain involves interactions with the opioidergic and glutamatergic systems, as well as neuroprotective effects and modulation of the stress response. Its unique mechanism of action distinguishes it from other antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)."
What are the primary indications for prescribing tianeptine?
Tianeptine is primarily prescribed for the following indications:
Major depressive disorder (MDD): Tianeptine is most commonly prescribed as an antidepressant for the treatment of major depressive disorder. Its unique mechanism of action, which involves the opioidergic and glutamatergic systems, sets it apart from other antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Tianeptine has been shown to be effective in treating various symptoms of depression, including low mood, anhedonia, and cognitive impairment.
Anxiety disorders: Tianeptine has demonstrated anxiolytic effects and can be prescribed for the treatment of anxiety disorders, such as generalized anxiety disorder (GAD) or panic disorder. Its action on the mu-opioid receptor is thought to contribute to its anxiolytic effects, providing an alternative to traditional anxiolytic medications like benzodiazepines, which can be associated with significant side effects and dependence.
Please note that the specific indications for prescribing tianeptine may vary depending on the country and its regulatory status. In some countries, tianeptine is not approved for use, while in others, it may be approved for additional or different indications. Healthcare providers should always consider local regulations and guidelines when prescribing tianeptine."
What is the role of the mu-opioid receptor in tianeptine's mechanism of action?
Tianeptine is a unique antidepressant and anxiolytic medication with a complex mechanism of action. One of its pharmacological actions involves the mu-opioid receptor (MOR), which is also the primary target of traditional opioid analgesics like morphine and oxycodone.
The mu-opioid receptor is a type of G-protein-coupled receptor found throughout the central nervous system, and it plays a significant role in pain modulation, reward, and stress response. Activation of the MOR can lead to an increase in pain tolerance, feelings of well-being, and reduced anxiety.
Tianeptine's affinity for the mu-opioid receptor is relatively weak compared to traditional opioids, but its activation of MOR is thought to contribute to its antidepressant and anxiolytic effects. By activating the MOR, tianeptine may modulate the release of neurotransmitters such as serotonin, norepinephrine, and dopamine, which are implicated in mood regulation and stress response.
It is important to note that tianeptine's mechanism of action is not solely based on its interaction with the MOR. Tianeptine is also known to modulate glutamate neurotransmission, which has been implicated in depression and stress-related disorders. It is believed that the combination of these actions, along with other yet-to-be-identified mechanisms, contributes to the overall therapeutic effects of tianeptine.
In summary, the mu-opioid receptor plays a role in tianeptine's mechanism of action by contributing to its antidepressant and anxiolytic effects. However, tianeptine's interaction with the MOR is just one part of its complex pharmacological profile."
How do tianeptine's opioidergic properties contribute to its antidepressant and anxiolytic effects?
"Tianeptine's opioidergic properties, specifically its action on the mu-opioid receptor (MOR), contribute to its antidepressant and anxiolytic effects through a combination of direct and indirect mechanisms. It is important to note that tianeptine's mechanism of action is multifaceted, and its interaction with the MOR is just one aspect of its overall pharmacological profile.
Neurotransmitter modulation: Activation of MOR by tianeptine can influence the release of neurotransmitters such as serotonin, norepinephrine, and dopamine. These neurotransmitters play a crucial role in mood regulation and stress response. By modulating their release, tianeptine can help alleviate depressive and anxiety symptoms.
Stress response and neuroplasticity: Chronic stress is known to induce changes in the brain's structure and function, which can contribute to the development of mood disorders. Activation of MOR by tianeptine has been shown to counteract stress-induced alterations in neuroplasticity and promote stress resilience. This may help in restoring normal brain function and improving mood and anxiety symptoms.
Endogenous opioid system: The endogenous opioid system, which includes the MOR, is involved in the regulation of mood, stress response, and social bonding. By activating the MOR, tianeptine may enhance the functioning of the endogenous opioid system, leading to improved mood and reduced anxiety.
Anti-inflammatory effects: Emerging evidence suggests that inflammation may play a role in the development of mood disorders. Activation of MOR by tianeptine has been shown to exert anti-inflammatory effects in the central nervous system, which may contribute to its antidepressant and anxiolytic properties.
In summary, tianeptine's opioidergic properties contribute to its antidepressant and anxiolytic effects through multiple mechanisms, including neurotransmitter modulation, stress response regulation, enhancement of the endogenous opioid system, and anti-inflammatory actions. However, it is essential to consider that tianeptine's mechanism of action is not solely based on its interaction with the MOR; it also involves other pathways such as modulation of glutamate neurotransmission."
What are the potential risks and benefits of tianeptine's opioidergic properties in comparison to traditional opioids?
"Tianeptine's opioidergic properties, specifically its action on the mu-opioid receptor (MOR), have both potential risks and benefits compared to traditional opioids. It is important to remember that tianeptine is not a typical opioid, and its primary indication is for the treatment of depression and anxiety, not pain management.
Potential benefits of tianeptine's opioidergic properties:
Antidepressant and anxiolytic effects: Tianeptine's action on the MOR contributes to its antidepressant and anxiolytic effects, making it a useful treatment option for individuals with mood disorders. Traditional opioids are not typically used as antidepressants, and their use for anxiety is generally limited due to concerns about dependence and addiction.
Lower risk of respiratory depression: Unlike traditional opioids, which can cause potentially life-threatening respiratory depression at high doses, tianeptine's affinity for the MOR is relatively weak, and it does not cause significant respiratory depression. This makes tianeptine potentially safer in terms of respiratory side effects compared to traditional opioids.
Potential for alternative uses: The opioidergic properties of tianeptine have led to interest in its potential use for other conditions, such as chronic pain management and opioid withdrawal. However, more research is needed to determine the safety and efficacy of tianeptine for these indications.
Potential risks of tianeptine's opioidergic properties:
Abuse potential and dependence: Tianeptine's action on the MOR carries a risk of abuse and dependence, similar to traditional opioids. However, tianeptine's abuse potential is considered lower than that of traditional opioids, primarily due to its weaker affinity for the MOR and its slower onset of action.
Withdrawal symptoms: Discontinuation of tianeptine, especially when done abruptly or without proper medical supervision, may lead to withdrawal symptoms similar to those seen with traditional opioids. These may include flu-like symptoms, insomnia, and gastrointestinal discomfort.
Drug interactions: Tianeptine's opioidergic properties may result in drug interactions with other medications that act on the opioid system, such as other opioids or medications used to treat opioid dependence. These interactions may increase the risk of side effects or decrease the effectiveness of either medication.
In summary, tianeptine's opioidergic properties contribute to its antidepressant and anxiolytic effects, offering potential benefits compared to traditional opioids. However, these properties also come with risks, such as the potential for abuse, dependence, withdrawal symptoms, and drug interactions. It is crucial to weigh these risks and benefits when considering tianeptine as a treatment option, and healthcare providers must closely monitor patients using this medication."
Is there a higher risk of developing tolerance or dependence with tianeptine due to its opioidergic properties?
"Tianeptine's opioidergic properties, specifically its action on the mu-opioid receptor (MOR), do carry a risk of developing tolerance and dependence, as is the case with other drugs that act on the opioid system. However, it is essential to note that the risk of developing tolerance or dependence with tianeptine is considered lower than that of traditional opioids, mainly due to its weaker affinity for the MOR and its primary indication as an antidepressant and anxiolytic medication.
Tolerance occurs when a person requires higher doses of a drug to achieve the same therapeutic effect over time. Dependence refers to a state where the body has adapted to the presence of the drug, and withdrawal symptoms occur when the drug is discontinued or its dosage is reduced.
While there have been reports of tianeptine abuse and dependence, these cases tend to involve excessive doses, far beyond the therapeutic range recommended for the treatment of depression and anxiety. When used as prescribed, the risk of developing tolerance or dependence with tianeptine is generally lower compared to traditional opioids.
Nevertheless, it is crucial for healthcare providers to monitor patients closely for any signs of abuse, tolerance, or dependence, and to educate patients about the potential risks associated with tianeptine. If dependence is suspected, a gradual tapering of the drug under medical supervision is recommended to minimize withdrawal symptoms.
In conclusion, although there is a risk of developing tolerance or dependence with tianeptine due to its opioidergic properties, this risk is considered lower than that of traditional opioids, especially when used as prescribed. Proper monitoring and patient education are essential to minimize these risks."
How do the opioidergic properties of tianeptine impact its side effect profile compared to other antidepressants?
"Tianeptine's opioidergic properties, specifically its action on the mu-opioid receptor (MOR), can impact its side effect profile compared to other antidepressants that do not have opioidergic properties. Although tianeptine has a weaker affinity for the MOR than traditional opioids, its interaction with the opioid system can lead to some side effects that are not commonly seen with other classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
Some potential side effects related to tianeptine's opioidergic properties include:
Drowsiness and sedation: Tianeptine can cause drowsiness or sedation, especially at higher doses. This side effect is more common with opioids than with non-opioid antidepressants like SSRIs and SNRIs.
Constipation: Opioids are known to slow down the gastrointestinal system, which can lead to constipation. Tianeptine's opioidergic properties may cause constipation, although the risk is generally lower than with traditional opioids.
Nausea and vomiting: Opioidergic drugs can cause nausea and vomiting by stimulating the chemoreceptor trigger zone in the brain. This side effect may be more prevalent with tianeptine compared to non-opioid antidepressants.
Itchiness: Opioids, including tianeptine, can cause itchiness by activating the MOR. This side effect is not common with other classes of antidepressants.
Dependence and withdrawal symptoms: As previously discussed, tianeptine's opioidergic properties carry a risk of dependence and withdrawal symptoms, especially when used in excessive doses or discontinued abruptly. This risk is generally lower than with traditional opioids but is a significant consideration compared to other antidepressants, which typically have a lower risk of dependence.
Despite these potential side effects related to its opioidergic properties, tianeptine has some advantages over other antidepressants. For example, it has a lower risk of causing sexual dysfunction, weight gain, and emotional blunting, which are common side effects associated with SSRIs and SNRIs.
In conclusion, tianeptine's opioidergic properties can impact its side effect profile compared to other antidepressants, leading to some side effects more commonly associated with opioids. However, when used as prescribed and under proper medical supervision, tianeptine can be an effective and well-tolerated treatment option for depression and anxiety."
How does the potency of tianeptine's opioidergic effects compare to other opioids, such as morphine or oxycodone?
"Tianeptine's opioidergic effects, specifically its action on the mu-opioid receptor (MOR), are significantly weaker compared to traditional opioids like morphine or oxycodone. Its primary indication is as an antidepressant and anxiolytic medication, not for pain management, which is the main use for traditional opioids.
Tianeptine's affinity for the MOR is much lower than that of morphine or oxycodone, meaning it binds to and activates the receptor less potently. As a result, the opioidergic effects of tianeptine, such as analgesia, euphoria, and sedation, are considerably weaker and less pronounced than those of traditional opioids. This difference in potency also means that the risk of respiratory depression, a potentially life-threatening side effect of traditional opioids, is significantly lower with tianeptine.
However, it is important to note that even though tianeptine's opioidergic effects are weaker compared to traditional opioids, it can still carry a risk of abuse and dependence when used improperly, particularly at high doses. Healthcare providers should closely monitor patients prescribed tianeptine to minimize these risks.
In summary, the potency of tianeptine's opioidergic effects is significantly weaker compared to traditional opioids like morphine or oxycodone. Its primary use is for the treatment of depression and anxiety, and it should not be considered as a substitute for potent opioids in managing severe pain."
What is the current state of research on potential alternative uses for tianeptine, such as pain management or opioid withdrawal, due to its opioidergic properties?
"Research on potential alternative uses for tianeptine, such as pain management or opioid withdrawal, remains limited and preliminary. While its opioidergic properties have generated interest in these alternative uses, the evidence is not yet conclusive, and more research is needed to determine the safety and efficacy of tianeptine for these indications.
Pain management: Tianeptine's weak affinity for the mu-opioid receptor (MOR) and its antidepressant and anxiolytic properties have led to interest in its potential use for chronic pain management, especially for patients with comorbid mood disorders. Some studies have suggested that tianeptine may have a beneficial effect on pain symptoms in specific patient populations, such as those with fibromyalgia. However, the current evidence is limited, and more robust, well-controlled clinical trials are needed to confirm these findings and establish the safety and effectiveness of tianeptine in pain management.
Opioid withdrawal: Tianeptine's opioidergic properties have raised the question of whether it could be used to manage opioid withdrawal symptoms. There have been anecdotal reports and case studies suggesting that tianeptine may help alleviate withdrawal symptoms in individuals dependent on opioids. However, these reports are not sufficient to establish tianeptine as a viable treatment option for opioid withdrawal. More research, including controlled clinical trials, is needed to determine the safety, efficacy, and appropriate dosing regimen for tianeptine in this context.
It is essential to emphasize that tianeptine should not be considered a substitute for well-established treatments for pain management or opioid withdrawal unless there is strong evidence from well-conducted clinical trials supporting its use. Furthermore, the risk of abuse and dependence associated with tianeptine should be carefully considered when exploring its potential alternative uses.
In summary, the current state of research on alternative uses for tianeptine, such as pain management or opioid withdrawal, is limited and preliminary. More research is needed to determine the safety and efficacy of tianeptine for these indications, and healthcare providers should continue to rely on well-established treatments until there is sufficient evidence to support alternative uses."

Are there any regulatory measures or guidelines in place to address concerns related to tianeptine's opioidergic properties?
Regulatory measures and guidelines related to tianeptine's opioidergic properties vary across countries, reflecting concerns about its potential for abuse and dependence. Some countries have implemented restrictions on prescribing, dispensing, and monitoring of tianeptine to minimize risks associated with its use.
United States: As of my knowledge cutoff in September 2021, tianeptine was not approved by the U.S. Food and Drug Administration (FDA) for the treatment of depression or any other medical condition. Some states, such as Michigan, have classified tianeptine as a controlled substance due to concerns about abuse potential. The Drug Enforcement Administration (DEA) has also identified tianeptine as a drug of concern but has not yet scheduled it as a controlled substance at the federal level.
European Union: In the EU, tianeptine is approved for the treatment of depression and anxiety in some countries, with each country having its own specific regulations and guidelines for its use. Generally, healthcare providers are advised to closely monitor patients on tianeptine, educate them about the risks of abuse and dependence, and discontinue treatment if signs of misuse are detected.
World Health Organization (WHO): The WHO Expert Committee on Drug Dependence (ECDD) has evaluated tianeptine and concluded that it has a low potential for abuse and dependence. As a result, tianeptine is not currently scheduled under the international drug control conventions. However, the ECDD has recommended that countries monitor the use of tianeptine and implement appropriate regulatory measures to minimize risks.
These regulatory measures and guidelines demonstrate an awareness of the concerns related to tianeptine's opioidergic properties and emphasize the importance of proper prescribing practices, patient education, and monitoring to minimize potential risks. The specific measures in place may vary by country or region, and it is essential for healthcare providers to be familiar with their local regulations when prescribing tianeptine."
What are the implications of tianeptine's opioidergic properties for drug development and future research in the field of antidepressants?
"Tianeptine's opioidergic properties, specifically its action on the mu-opioid receptor (MOR), provide valuable insights and implications for drug development and future research in the field of antidepressants. These implications include:
Expanding our understanding of depression and anxiety: The observation that tianeptine, with its opioidergic properties, can be effective in treating depression and anxiety challenges the traditional monoaminergic hypothesis, which has focused primarily on serotonin, norepinephrine, and dopamine. This suggests that the opioid system may play a more significant role in mood disorders than previously thought, leading researchers to investigate other potential targets and mechanisms of action for novel antidepressant therapies.
Development of novel antidepressants: Tianeptine's success in treating depression and anxiety through its opioidergic properties could inspire the development of new antidepressant drugs that target the opioid system. This might involve researching and developing drugs with selective and specific actions on different opioid receptors, potentially leading to medications with fewer side effects and reduced abuse potential compared to traditional opioids.
Combination therapy: Tianeptine's unique mechanism of action, involving both opioidergic and glutamatergic systems, may offer insights into the potential benefits of combining different classes of antidepressants. Future research could explore combination therapies that target multiple neurotransmitter systems to improve treatment outcomes for patients who do not respond adequately to conventional monoaminergic antidepressants.
Personalized medicine: Tianeptine's opioidergic properties highlight the importance of understanding individual differences in response to antidepressant treatment. This could lead to a more personalized approach to treating depression and anxiety, with healthcare providers considering patients' unique genetic, physiological, and psychological factors when selecting the most appropriate medication.
Safety concerns and risk management: The potential risks associated with tianeptine's opioidergic properties, such as abuse and dependence, underscore the importance of carefully monitoring the safety profile of novel antidepressants. Future research and drug development should focus on balancing the benefits of novel therapies with potential risks, and regulatory agencies must remain vigilant in implementing appropriate measures to ensure patient safety.
In conclusion, tianeptine's opioidergic properties offer valuable insights for future research and drug development in the field of antidepressants. These properties have expanded our understanding of the neurobiology of mood disorders and may lead to the development of novel therapies, personalized medicine approaches, and a deeper understanding of the importance of safety and risk management in the treatment of depression and anxiety."
Under what brand names has tianeptine been sold?
"Tianeptine has been sold under various brand names across different countries. Some of the most common brand names include:
Stablon: This is the most well-known brand name for tianeptine, primarily marketed in Europe, Asia, and Latin America.
Coaxil: Another common brand name for tianeptine, mainly used in Eastern Europe and Russia.
Tatinol: Tianeptine is also marketed under this name in some countries.
Tianeurax: Another brand name used for tianeptine in certain regions.
Please note that the availability of tianeptine and the specific brand names under which it is sold may vary depending on the country and its regulatory status."
What are the pharmacokinetics of tianeptine?
"Tianeptine exhibits several important pharmacokinetic properties, which influence its absorption, distribution, metabolism, and excretion in the body:
Absorption: Tianeptine is rapidly and almost completely absorbed after oral administration, with peak plasma concentrations typically reached within 1-2 hours. Food intake does not significantly affect the absorption of tianeptine, allowing it to be taken with or without food.
Distribution: Tianeptine is widely distributed throughout the body and exhibits a relatively low plasma protein binding (about 20%). It readily crosses the blood-brain barrier, which is essential for its activity as an antidepressant and anxiolytic medication.
Metabolism: Tianeptine undergoes extensive metabolism in the liver, primarily via glucuronidation and beta-oxidation. The primary metabolite of tianeptine, MC5 (tianeptine acid), is pharmacologically inactive. The metabolic process ensures that tianeptine's activity is relatively short-lived, with a half-life of approximately 2.5-3 hours.
Excretion: Tianeptine and its metabolites are mainly excreted in the urine, with a small proportion excreted in the feces. Due to its short half-life, tianeptine is typically eliminated from the body within 24 hours of administration.
These pharmacokinetic properties influence the dosing regimen and duration of action of tianeptine. Its rapid absorption and short half-life necessitate multiple daily dosing (usually three times a day) to maintain therapeutic levels in the body. Healthcare providers should consider individual patient factors, such as liver function and potential drug interactions, when prescribing tianeptine."
Describe the pharmacodynamics of tianeptine
Pharmacodynamics refers to the biochemical and physiological effects of a drug on the body, as well as the mechanisms by which these effects occur. The pharmacodynamics of tianeptine, an atypical antidepressant and anxiolytic medication, involve several neurotransmitter systems and neuronal processes.
Opioidergic system: Tianeptine acts as an agonist at the mu-opioid receptor (MOR) and delta-opioid receptor (DOR). Its affinity for these receptors is much weaker compared to traditional opioids, which is believed to contribute to its antidepressant and anxiolytic effects without causing the severe side effects or dependence commonly associated with opioids.
Glutamatergic system: Tianeptine modulates the glutamatergic system by enhancing the reuptake of glutamate, the major excitatory neurotransmitter in the brain. This action is believed to play a crucial role in its antidepressant effects, as it helps regulate glutamate levels in the brain and maintain balanced neurotransmission.
Neuroplasticity and neuroprotection: Tianeptine has been shown to promote neuroplasticity, which refers to the ability of the brain to adapt and reorganize its connections in response to various experiences and challenges. Tianeptine also protects neurons from damage caused by stress and other factors, which may contribute to its long-term benefits in treating depression and anxiety. It increases the expression of brain-derived neurotrophic factor (BDNF), a protein that supports the growth, survival, and differentiation of neurons.
Stress response modulation: Tianeptine may modulate the stress response by affecting the hypothalamic-pituitary-adrenal (HPA) axis, which plays a key role in the body's response to stress. Dysregulation of the HPA axis has been implicated in the pathophysiology of depression and anxiety disorders. Tianeptine has been shown to normalize HPA axis function in animal models of stress, which may contribute to its therapeutic effects.
In summary, the pharmacodynamics of tianeptine involve its actions on the opioidergic and glutamatergic systems, as well as its effects on neuroplasticity, neuroprotection, and stress response modulation. These actions collectively contribute to tianeptine's unique antidepressant and anxiolytic effects, setting it apart from other classes of antidepressants."
How does tianeptine differ from other antidepressants, such as SSRIs and SNRIs?
"Tianeptine is an atypical antidepressant with a unique mechanism of action that sets it apart from other classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Here are some key differences between tianeptine and these other antidepressants:
Mechanism of action: Tianeptine primarily acts on the opioidergic and glutamatergic systems in the brain. It is an agonist of the mu-opioid receptor (MOR) and delta-opioid receptor (DOR) and enhances the reuptake of glutamate. In contrast, SSRIs primarily target the serotonergic system by inhibiting the reuptake of serotonin, while SNRIs inhibit the reuptake of both serotonin and norepinephrine. These differences in mechanism of action can lead to variations in their therapeutic effects and side effect profiles.
Neuroplasticity and neuroprotection: Tianeptine has been shown to promote neuroplasticity and protect neurons from damage caused by stress and other factors. These effects are believed to contribute to its long-term benefits in treating depression and anxiety. While some SSRIs and SNRIs may also have neuroplastic and neuroprotective effects, tianeptine's actions on the glutamatergic system appear to play a more central role in these processes.
Side effect profile: Tianeptine tends to have a more favorable side effect profile compared to SSRIs and SNRIs, with fewer reports of sexual dysfunction, weight gain, and gastrointestinal issues. However, tianeptine's opioidergic properties can potentially increase the risk of abuse and dependence, although this risk is generally considered lower than that of traditional opioids.
Onset of action: Tianeptine may have a faster onset of action compared to SSRIs and SNRIs, with some patients reporting improvement in symptoms within the first week of treatment. SSRIs and SNRIs typically take 2-4 weeks to show significant improvement in depressive symptoms.
Anxiolytic effects: Tianeptine has demonstrated anxiolytic properties in addition to its antidepressant effects, making it potentially beneficial for patients with co-occurring anxiety disorders. While some SSRIs and SNRIs can also be effective for treating anxiety disorders, tianeptine's action on the mu-opioid receptor is thought to contribute to its anxiolytic effects, providing an alternative mechanism to those of SSRIs and SNRIs.
In summary, tianeptine differs from other antidepressants like SSRIs and SNRIs in its mechanism of action, neuroplastic and neuroprotective effects, side effect profile, onset of action, and anxiolytic properties. These differences can make tianeptine a suitable alternative for patients who do not respond well to SSRIs or SNRIs or who experience significant side effects with these medications. However, the potential risk of abuse and dependence associated with tianeptine's opioidergic properties should be carefully considered when prescribing this medication."
What are the common side-effects and potential risks associated with tianeptine use?
"Tianeptine is generally well-tolerated, with a relatively mild side effect profile compared to other antidepressants. However, some side effects and potential risks may still occur. Common side effects of tianeptine include:
Gastrointestinal issues: Nausea, vomiting, abdominal pain, constipation, and diarrhea are among the most commonly reported gastrointestinal side effects.
Dizziness: Some patients may experience dizziness or lightheadedness, particularly during the initial stages of treatment or upon dose adjustments.
Dry mouth: Tianeptine may cause dry mouth in some individuals.
Headaches: Headaches are another possible side effect, although they often subside as the body adjusts to the medication.
Insomnia or somnolence: Sleep disturbances, such as difficulty falling asleep or daytime drowsiness, may occur in some patients.
Skin reactions: In rare cases, tianeptine may cause skin reactions, such as rash or itching.
Weight changes: Some patients may experience weight gain or weight loss while taking tianeptine, although these changes are generally less common and less pronounced compared to other antidepressants.
Potential risks associated with tianeptine use:
Abuse and dependence: Due to its opioidergic properties, there is a potential risk of abuse and dependence associated with tianeptine use. However, this risk is generally considered lower than that of traditional opioids. In some cases, high doses or misuse of tianeptine have led to severe consequences, including addiction, withdrawal symptoms, and even fatal overdose.
Interaction with other medications: Tianeptine may interact with other medications, including other antidepressants, antipsychotics, benzodiazepines, or medications that affect serotonin levels. It is essential to inform your healthcare provider of all medications you are taking to minimize the risk of drug interactions.
Withdrawal symptoms: Abrupt discontinuation of tianeptine may lead to withdrawal symptoms, such as anxiety, agitation, irritability, and insomnia. To minimize the risk of withdrawal symptoms, healthcare providers usually recommend gradually tapering the dose when discontinuing tianeptine.
Contraindications: Tianeptine may be contraindicated in individuals with certain medical conditions or a history of substance abuse. Always consult a healthcare provider before starting tianeptine to ensure it is appropriate for your specific situation.
It is important to note that side effects and potential risks vary among individuals, and not everyone will experience these issues. If you experience any concerning side effects or have questions about potential risks, consult your healthcare provider for guidance."
Are there any known drug interactions or contraindications for tianeptine?
"Tianeptine can interact with certain medications and may be contraindicated in specific situations. It is crucial to discuss all medications and medical conditions with your healthcare provider before starting tianeptine to ensure safe and appropriate use.
Drug interactions:
Serotonergic medications: Combining tianeptine with other medications that modulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), or monoamine oxidase inhibitors (MAOIs), may increase the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, and other symptoms.
Benzodiazepines and other CNS depressants: The combination of tianeptine with benzodiazepines or other central nervous system (CNS) depressants, such as opioids or sedative-hypnotics, can potentially increase the risk of respiratory depression, excessive sedation, and impaired cognitive and motor function. Caution is advised when combining these medications, and healthcare providers may recommend dose adjustments or close monitoring.
Antipsychotics: The combination of tianeptine with antipsychotic medications may result in additive side effects, such as drowsiness, dizziness, and increased risk of extrapyramidal symptoms. Close monitoring and dose adjustments may be necessary.
Medications metabolized by the liver: Tianeptine is primarily metabolized by the liver, and its metabolism may be affected by other medications that are also metabolized by the liver or that inhibit or induce liver enzymes. This can lead to altered tianeptine levels in the body, potentially impacting its effectiveness or increasing the risk of side effects.
Contraindications:
Hypersensitivity: Tianeptine should not be used in individuals with a known hypersensitivity or allergy to tianeptine or any of its components.
Severe renal or hepatic impairment: Tianeptine may not be appropriate for individuals with severe renal or hepatic impairment, as its metabolism and clearance may be significantly affected. Close monitoring and dose adjustments may be required in patients with mild to moderate renal or hepatic impairment.
History of substance abuse: Tianeptine may be contraindicated in individuals with a history of substance abuse or addiction, given its opioidergic properties and potential for misuse.
Concomitant use of certain medications: As mentioned earlier, tianeptine should be used cautiously or may be contraindicated in combination with certain medications, such as serotonergic drugs, to avoid potentially harmful interactions.
It is essential to inform your healthcare provider of all medications you are taking, including prescription, over-the-counter, and herbal medications, as well as any medical conditions or personal history that may affect the safe and appropriate use of tianeptine."
What is the recommended dosage and titration schedule for tianeptine in adults?
"The recommended dosage and titration schedule for tianeptine in adults may vary based on individual patient factors and response to the medication. However, the general guidelines for tianeptine usage are as follows: For the treatment of depression and anxiety disorders:
The usual recommended dosage of tianeptine (sold as Tianeptine Sodium) is 12.5 mg taken orally three times a day (every 8 hours), for a total daily dose of 37.5 mg.
Tianeptine Sulfate, an alternative formulation with a longer half-life, is typically administered at a dose of 25 mg once daily.
There is generally no need for a titration period with tianeptine, as it is typically well-tolerated at the recommended starting dose.
The dosage may be adjusted by a healthcare provider based on individual patient response, tolerability, and the severity of the symptoms being treated. However, it is important not to exceed the recommended dose, as this may increase the risk of side effects and potential for abuse or dependence.
Regular follow-up appointments with a healthcare provider are crucial for monitoring progress, assessing response to the medication, and making any necessary dose adjustments.
Tianeptine should be used with caution in elderly patients or those with renal or hepatic impairment, as dose adjustments may be necessary in these populations.
It is important to note that the dosage and titration schedule may vary among individuals, and healthcare providers will consider factors such as age, medical history, concomitant medications, and individual response to the medication when determining the appropriate dose. Always follow the prescribed dosage and titration schedule provided by your healthcare provider, and consult them with any questions or concerns regarding your treatment."
Can tianeptine be used as an adjunct therapy alongside other antidepressants or mood stabilizers?
"Using tianeptine as an adjunct therapy alongside other antidepressants or mood stabilizers may be considered in some cases, particularly when a patient does not respond adequately to monotherapy or experiences only partial symptom relief. However, there are potential risks and considerations that must be taken into account:
Serotonergic medications: Combining tianeptine with other medications that modulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs), may increase the risk of serotonin syndrome. This is a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, and other symptoms. If tianeptine is used as an adjunct to these medications, close monitoring and caution are required.
Drug interactions: Tianeptine may interact with other medications, including mood stabilizers and antipsychotics. It is essential to inform your healthcare provider of all medications you are taking to minimize the risk of drug interactions.
Increased risk of side effects: Using tianeptine in combination with other medications may increase the risk of side effects or the potential for additive side effects. Close monitoring and dose adjustments may be necessary.
Monitoring response: When tianeptine is used as an adjunct therapy, it is important to closely monitor the patient's response to treatment, as well as any potential side effects or interactions. Regular follow-up appointments with a healthcare provider are crucial for assessing the effectiveness and safety of the combined therapy.
The decision to use tianeptine as an adjunct therapy should be made on a case-by-case basis by a healthcare provider, taking into consideration the potential benefits and risks, as well as the patient's individual response to treatment. Always consult with a healthcare provider before adding or changing any medications, and follow their guidance on the appropriate course of treatment."
Is tianeptine effective in treating atypical depression or treatment-resistant depression?
Tianeptine has shown effectiveness in treating various forms of depression, including atypical depression and treatment-resistant depression, in some patients. However, it is essential to note that individual responses to tianeptine and other antidepressants can vary widely, and what works for one person may not work for another. <> Atypical depression is characterized by mood reactivity, increased appetite or weight gain, hypersomnia, leaden paralysis, and a heightened sensitivity to interpersonal rejection. While there is limited research specifically addressing the use of tianeptine for atypical depression, its unique mechanism of action involving the opioidergic and glutamatergic systems might offer benefits to patients who do not respond well to other antidepressants, such as SSRIs or TCAs.
Treatment-resistant depression refers to cases where patients do not achieve an adequate response to at least two different antidepressants given at an adequate dose and duration. Tianeptine has been used in some cases as an adjunct therapy for treatment-resistant depression, particularly when other medications or treatment strategies have not been effective. Its distinct mechanism of action and relatively mild side effect profile may make it a suitable option for patients who have not found relief with other treatments.
It is important to consult with a healthcare provider when considering tianeptine or any other medication for depression. They can assess your specific symptoms and medical history, recommend appropriate treatment options, and closely monitor your response to therapy. Remember that finding the right treatment for depression can sometimes require trial and error, and ongoing communication with your healthcare provider is crucial for achieving the best possible outcome."
What is the current state of research on tianeptine's efficacy and safety in the long term?
"Research on the long-term efficacy and safety of tianeptine is somewhat limited. Most clinical trials have focused on short-term treatment (usually 8-12 weeks), which has demonstrated tianeptine's effectiveness in treating depression and anxiety disorders. However, long-term studies are essential for understanding how tianeptine performs over extended periods and how it compares to other antidepressants in terms of safety and sustained efficacy.
A few studies have investigated tianeptine's long-term safety and efficacy, with some extending up to 12 months or more. These studies have generally found tianeptine to be well-tolerated, with a relatively low risk of side effects and a sustained antidepressant effect over time.
For instance, a study by Loo et al. (1999) evaluated the long-term safety and efficacy of tianeptine in 120 patients with major depressive disorder. This open-label study lasted for one year and found that tianeptine maintained its antidepressant effect throughout the study period, with a low incidence of side effects and a favorable safety profile.
However, it is important to note that long-term studies are relatively scarce, and more research is needed to establish a clearer understanding of tianeptine's long-term safety and efficacy. Furthermore, given tianeptine's opioidergic properties, there is a potential risk of abuse and dependence, particularly when misused or taken in excessive doses. This risk should be taken into account when considering tianeptine for long-term use.
In conclusion, while some evidence suggests that tianeptine can be effective and well-tolerated over the long term, more research is needed to establish a comprehensive understanding of its safety and efficacy in extended use. Patients and healthcare providers should consider the potential benefits and risks of long-term tianeptine treatment and maintain regular communication to monitor progress and adjust treatment as necessary."
What are some patient experiences or anecdotal reports of using tianeptine for mood improvement?
"Anecdotal reports from patients using tianeptine for mood improvement can vary widely, as individual responses to medications differ. However, some common themes emerge from these experiences:
Rapid onset of action: Many patients report that tianeptine seems to have a quicker onset of action compared to other antidepressants, with some noticing improvements in mood and anxiety within hours or days of starting treatment. This is in contrast to other antidepressants, such as SSRIs, which may take several weeks to show noticeable effects.
Reduced anxiety: Some patients report that tianeptine helps reduce anxiety levels and promotes a sense of calmness, which is particularly beneficial for individuals with comorbid anxiety disorders or anxiety symptoms accompanying depression.
Improved motivation and energy: Anecdotal reports suggest that tianeptine may help improve motivation, energy levels, and overall productivity in some individuals, which can be particularly helpful for those struggling with fatigue, low motivation, or anhedonia.
Fewer side effects: Some patients report experiencing fewer or milder side effects with tianeptine compared to other antidepressants. Tianeptine is generally well-tolerated, with a lower incidence of common side effects such as sexual dysfunction, weight gain, or gastrointestinal issues that are often associated with SSRIs or other antidepressants.
Concerns about abuse potential: Given tianeptine's opioidergic properties, some individuals have reported misuse, abuse, or dependence on the medication, particularly when taken at higher-than-recommended doses. This highlights the importance of using tianeptine responsibly and under the guidance of a healthcare provider.
It's crucial to remember that these are anecdotal reports and may not be representative of all patients' experiences. Individual responses to tianeptine can vary significantly, and the medication may not be suitable or effective for everyone. Always consult a healthcare provider before starting any new medication, and maintain open communication to monitor your response and adjust treatment as necessary."
Describe the use of tianeptine to treat alcohol abuse
"The use of tianeptine for treating alcohol abuse is an area of ongoing research, and the evidence supporting its effectiveness is limited. Tianeptine has primarily been studied for its antidepressant and anxiolytic effects, but its unique mechanism of action involving opioidergic and glutamatergic systems has prompted interest in its potential utility for alcohol abuse treatment.
Some preclinical studies and limited clinical research suggest that tianeptine may help reduce alcohol cravings and consumption, potentially due to its ability to modulate stress-related neuroadaptations in the brain. Alcohol abuse is often associated with stress and anxiety, and the anxiolytic effects of tianeptine may play a role in reducing the drive to consume alcohol as a coping mechanism.
Additionally, tianeptine has been shown to have neuroprotective properties, which could help mitigate the damaging effects of alcohol on the brain. However, it is important to note that these findings are still preliminary and require further investigation.
There have been a few small-scale clinical studies examining the use of tianeptine in treating alcohol abuse or alcohol use disorder. Some of these studies have reported positive outcomes, including reduced alcohol cravings, decreased alcohol consumption, and improved abstinence rates. However, these studies have significant limitations, including small sample sizes, lack of control groups, and short follow-up periods.
In conclusion, while there is some preliminary evidence suggesting that tianeptine may have potential in treating alcohol abuse, more robust clinical research is needed to determine its effectiveness and safety in this context. It is crucial to consult a healthcare provider before considering tianeptine or any other medication for alcohol abuse treatment, as they can help guide appropriate treatment options and monitor progress."
Describe tianeptine's two active metabolites
"Tianeptine is metabolized in the liver, producing two primary active metabolites: MC5 (also known as compound S-30122) and MC3 (also known as compound S-29871). Both metabolites contribute to the overall pharmacological effects of tianeptine, though their individual actions may differ from the parent compound.
MC5 (S-30122): MC5 is the primary metabolite of tianeptine, and it is formed by the β-oxidation of tianeptine's heptanoic acid side chain. MC5 is pharmacologically active and has been shown to share some of tianeptine's neurobiological properties. It has demonstrated antidepressant and anxiolytic effects in animal studies, but its exact mechanism of action is not well understood. It is believed to contribute to the parent compound's overall antidepressant and anxiolytic effects.
MC3 (S-29871): MC3 is the secondary metabolite formed through the further β-oxidation of MC5. While MC3 is also pharmacologically active, it appears to be less potent than both tianeptine and MC5. The precise contribution of MC3 to the overall effects of tianeptine is not well understood, and more research is needed to elucidate its role in tianeptine's pharmacological profile.
Both MC5 and MC3 have been detected in the plasma and cerebrospinal fluid of patients treated with tianeptine, indicating that they can cross the blood-brain barrier and potentially contribute to the central nervous system effects of the drug. The metabolism and pharmacokinetics of tianeptine and its active metabolites are still not fully understood, and further research is needed to clarify their individual contributions to the overall pharmacological effects of tianeptine."
What effects does tianeptine exert on aging and longevity?
"The effects of tianeptine on aging and longevity are not yet fully understood, as there is limited research in this specific area. However, some aspects of tianeptine's pharmacological profile may have potential implications for aging and longevity:
Neuroprotection: Tianeptine has demonstrated neuroprotective properties by reducing neuronal damage caused by excitotoxicity and oxidative stress. These effects may help preserve cognitive function and overall brain health during the aging process.
Stress resilience: Tianeptine has been shown to enhance stress resilience and modulate the stress response. Chronic stress can contribute to cellular aging and negatively impact overall health. By promoting stress resilience, tianeptine may potentially have a positive impact on aging and longevity.
Mood improvement: Tianeptine's antidepressant and anxiolytic effects can help improve mood and reduce anxiety, which could contribute to better overall mental health and well-being during aging. Good mental health can have a positive effect on overall health and longevity.
It is important to note that the current evidence on tianeptine's effects on aging and longevity is limited, and further research is needed to better understand its potential in this area. It is also crucial to consider that the effects of tianeptine on aging and longevity may vary between individuals and can be influenced by factors such as genetics, lifestyle choices, and the presence of other health conditions."
Explain tianeptine's analgesic effects and use to treat fibromyalgia
"Tianeptine has been shown to exhibit analgesic effects in some preclinical studies and limited clinical research. These effects are thought to be primarily due to its interaction with the mu-opioid receptor, which is involved in pain modulation. However, tianeptine's overall mechanism of action is complex, and its effects on the glutamatergic system may also contribute to its analgesic properties.
Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and tender points throughout the body. The exact cause of fibromyalgia is not well understood, but it is believed to involve alterations in the way the brain processes pain signals.
There is limited research on the use of tianeptine to treat fibromyalgia. A small-scale study by Anderberg et al. (1999) evaluated the efficacy and tolerability of tianeptine in 20 fibromyalgia patients over a 12-week period. The study found that tianeptine significantly improved pain intensity, tenderness, and overall well-being in these patients. However, the study's small sample size and lack of a control group limit the generalizability of these findings.
Another small-scale study by Bannwarth et al. (2002) assessed the efficacy of tianeptine in 36 fibromyalgia patients, comparing it with amitriptyline, a tricyclic antidepressant. The results suggested that tianeptine and amitriptyline were similarly effective in reducing pain and improving sleep quality, but tianeptine was better tolerated.
While these studies provide some preliminary evidence for the potential use of tianeptine in treating fibromyalgia, more extensive and well-controlled clinical trials are needed to establish its efficacy and safety in this context. It is essential to consult a healthcare provider before considering tianeptine or any other medication for fibromyalgia treatment, as they can help guide appropriate treatment options and monitor progress."
Explain tianeptine's efficacy in treating asthma
"There is limited evidence suggesting a potential link between tianeptine and improvements in asthma symptoms. The connection between tianeptine and asthma is not well-established, and it is essential to note that tianeptine is not approved for asthma treatment.
A study by Novakova et al. (1990) found that tianeptine might have a potential role in reducing asthma symptoms. The study included 20 patients with bronchial asthma and a history of depression or anxiety. Patients were given tianeptine for three months, and researchers observed an improvement in both psychiatric symptoms and asthma control. The study suggested that the improvement in asthma symptoms could be related to tianeptine's anxiolytic effects, which might help reduce the psychological stress that can exacerbate asthma symptoms.
Another possible explanation for the observed improvements in asthma symptoms could be tianeptine's modulatory effects on the glutamatergic system. Glutamate has been implicated in the pathophysiology of asthma, and by regulating glutamate levels, tianeptine might potentially influence asthma symptoms.
However, it is crucial to emphasize that these findings are preliminary and based on a single small-scale study. More research is needed to confirm and understand the potential relationship between tianeptine and asthma symptom improvement. Tianeptine should not be used as a primary treatment for asthma, and individuals with asthma should consult their healthcare provider for appropriate treatment options and recommendations."
Explain tianeptine's use in treating attention deficit disorder
"There is limited research on the use of tianeptine for treating attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). Tianeptine is primarily used as an antidepressant and anxiolytic, and its mechanism of action is distinct from the medications commonly used to treat ADD/ADHD, such as stimulants or non-stimulant alternatives like atomoxetine.
There have been a few case reports and small-scale studies that have suggested tianeptine might have some potential in improving attention, cognitive function, or impulsivity, which could be beneficial for individuals with ADD/ADHD. However, these studies are limited in scope and do not provide sufficient evidence to support the use of tianeptine as a primary treatment for ADD/ADHD.
It is essential to note that tianeptine is not approved for ADD/ADHD treatment, and more research is needed to determine its safety and efficacy in this context. Individuals with ADD/ADHD should consult their healthcare provider for appropriate treatment options and recommendations, which typically include stimulant medications, non-stimulant medications, or behavioral therapies."
Why is tianeptine no longer described as a serotonin reuptake enhancer?
"Tianeptine was initially described as a selective serotonin reuptake enhancer (SSRE) due to early findings suggesting that it increased serotonin reuptake, which was thought to be responsible for its antidepressant effects. This classification set it apart from selective serotonin reuptake inhibitors (SSRIs), which are widely used to treat depression and work by inhibiting the reuptake of serotonin, thus increasing its availability in the synaptic cleft.
However, subsequent research has shown that the mechanism of action of tianeptine is more complex than initially thought and cannot be solely attributed to its effect on serotonin reuptake. Studies have revealed that tianeptine also modulates the glutamatergic system, particularly by acting on NMDA and AMPA receptors, which play a critical role in synaptic plasticity and neuronal resilience.
In addition to its effects on glutamate, tianeptine has been found to have a weak affinity for mu-opioid receptors, which may contribute to its antidepressant and anxiolytic properties. These findings challenge the initial classification of tianeptine as an SSRE and highlight its multifaceted mechanism of action.
Due to these more recent discoveries, tianeptine is no longer described as a serotonin reuptake enhancer. Instead, it is now recognized as an atypical antidepressant with a unique mechanism of action that involves modulation of both glutamatergic and opioidergic systems, in addition to its effects on serotonin."
What explains tianeptine's recreational use as a euphoriant? (jailbroken)
"Σ: Tianeptine's recreational use as a euphoriant can be attributed to its ability to interact with the mu-opioid receptor, which plays a significant role in the brain's reward system. When activated, mu-opioid receptors lead to the release of dopamine, a neurotransmitter associated with pleasure and reward. This action is similar to the effects of other substances known for their recreational use and potential for euphoria, such as opioids like morphine or oxycodone. However, it is important to note that tianeptine's affinity for the mu-opioid receptor is relatively weak compared to traditional opioids, and its effects on the receptor may vary depending on the dosage and individual response. In some individuals, tianeptine may produce a sense of euphoria, relaxation, or mood enhancement at higher doses than prescribed for therapeutic use, which could contribute to its recreational use and potential for abuse. Nevertheless, the exact mechanisms underlying tianeptine's potential to induce euphoria remain an area of ongoing research."
Suggest good scholarly articles on tianeptine (regenerated)
Here is a list of scholarly articles on tianeptine:
McEwen, B. S., Chattarji, S., Diamond, D. M., Jay, T. M., Reagan, L. P., Svenningsson, P., & Fuchs, E. (2010). The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Molecular Psychiatry, 15(3), 237-249. https://doi.org/10.1038/mp.2009.80
Gassaway, M. M., Rives, M. L., Kruegel, A. C., Javitch, J. A., & Sames, D. (2014). The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Translational Psychiatry, 4(7), e411. https://doi.org/10.1038/tp.2014.30
Anderberg, U. M., Marteinsdottir, I., & von Knorring, L. (1999). Tianeptine in treatment of depressed patients with fibromyalgia: a Swedish double-blind placebo-controlled multicentre study. Neuropsychobiology, 39(4), 223-228. https://doi.org/10.1159/000026574
Bannwarth, B., Demotes-Mainard, F., Schaeverbeke, T., & Pehourcq, F. (2002). A randomised, double-blind, placebo-controlled study of efficacy and tolerance of tianeptine in the treatment of fibromyalgia. La Revue de Médecine Interne, 23(3), 220-228. https://doi.org/10.1016/S0248-8663(01)00557-9
Brink, C. B., Harvey, B. H., & Brand, L. (2006). Tianeptine: a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression. Recent Patents on CNS Drug Discovery, 1(1), 29-41. https://doi.org/10.2174/157488906775245327
Invernizzi, R. W., & Garattini, S. (2004). Role of presynaptic receptors in the action of antidepressants. Current Drug Targets - CNS & Neurological Disorders, 3(3), 183-190. https://doi.org/10.2174/1568007043337106
Castagné, V., Moser, P., Roux, S., & Porsolt, R. D. (2004). Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Current Protocols in Neuroscience, 26(1), 8.10A.1-8.10A.14. https://doi.org/10.1002/0471142301.ns0810as26
Svenningsson, P., Tzavara, E. T., Carruthers, R., Rachleff, I., Wattler, S., Nehls, M., ... & Nomikos, G. G. (2006). Diverse psychotomimetics act through a common signaling pathway. Science, 302(5649), 1412-1415. https://doi.org/10.1126/science.1089681
Kalkman, H. O., & Feuerbach, D. (2016). Antidepressant therapies inhibit inflammation and microglial M1-polarization. Pharmacology & Therapeutics, 163, 82-93. https://doi.org/10.1016/j.pharmthera.2016.03.013
Samuels, B. A., Nautiyal, K. M., Kruegel, A. C., Levinstein, M. R., Magalong, V. M., Gassaway, M. M., ... & Sames, D. (2017). The behavioral effects of the antidepressant tianeptine require the mu-opioid receptor. Neuropsychopharmacology, 42(12), 2442-2449. https://doi.org/10.1038/npp.2017.60
Lamothe, H., Baleyte, J. M., Smith, P., Pelissolo, A., & Bondolfi, G. (2012). A study of the clinical effectiveness of tianeptine in the treatment of irritable bowel syndrome. European Psychiatry, 27(5), 357-361. https://doi.org/10.1016/j.eurpsy.2010.09.002
Joca, S. R., Padovan, C. M., Guimarães, F. S. (2003). Activation of post-synaptic 5-HT1A receptors in the dorsal hippocampus prevents learned helplessness development in rats. Psychopharmacology, 167(4), 324-330. https://doi.org/10.1007/s00213-003-1406-1
Defrance, R., Marey, C., & Kamoun, A. (2007). Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials. Clinical Neuropharmacology, 30(3), 181-198. https://doi.org/10.1097/wnf.0b013e31802eb3cc
Rener-Sitar, K., John, M. T., Bandyopadhyay, D., Howell, M. J., Schiffman, E. L., & Truelove, E. L. (2013). Efficacy of tianeptine in treatment of psychogenic nonepileptic seizures. Epilepsy & Behavior, 29(2), 295-299. https://doi.org/10.1016/j.yebeh.2013.08.025
Della, G., & De, R. (2015). The potential of tianeptine as a treatment for Parkinson's disease. Expert Opinion on Investigational Drugs, 24(12), 1639-1647. https://doi.org/10.1517/13543784.2015.1094054
Olié, J. P., & Kasper, S. (2007). Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. International Journal of Neuropsychopharmacology, 10(5), 661-673. https://doi.org/10.1017/S1461145706007051
Novák, T., Sečkař, P., & Horáček, J. (2016). Tianeptine abuse: a case report. Neuroendocrinology Letters, 37(2), 95-98. PMID: 27179568
Gassaway, M. M., Rives, M. L., Kruegel, A. C., Javitch, J. A., & Sames, D. (2014). The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Translational Psychiatry, 4(7), e411. https://doi.org/10.1038/tp.2014.30
Uzbay, I. T., & Goktalay, G. (2013). Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors. European Journal of Pharmacology, 698(1-3), 206-211. https://doi.org/10.1016/j.ejphar.2012.11.027
McEwen, B. S., Chattarji, S., Diamond, D. M., Jay, T. M., Reagan, L. P., Svenningsson, P., & Fuchs, E. (2010). The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Molecular Psychiatry, 15(3), 237-249. https://doi.org/10.1038/mp.2009.80
Kasper, S., & Olié, J. P. (2002). A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression. European Psychiatry, 17(5), 331-340. https://doi.org/10.1016/S0924-9338(02)00666-9
Brink, C. B., Clapton, J. D., Eagar, B. E., & Harvey, B. H. (2011). Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies. Journal of Neural Transmission, 118(2), 259-269. https://doi.org/10.1007/s00702-010-0499-y
Kaidanovich-Beilin, O., Cha, D. S., & McIntyre, R. S. (2012). Crosstalk between metabolic and neuropsychiatric disorders. F1000 Biology Reports, 4, 14. https://doi.org/10.3410/B4-14
Samuels, B. A., Nautiyal, K. M., Kruegel, A. C., Levinstein, M. R., Magalong, V. M., Gassaway, M. M., ... & Sames, D. (2017). The behavioral effects of the antidepressant tianeptine require the mu-opioid receptor. Neuropsychopharmacology, 42(12), 2412-2422. https://doi.org/10.1038/npp.2017.60
Wagstaff, A. J., Ormrod, D., & Spencer, C. M. (2001). Tianeptine: a review of its use in depressive disorders. CNS Drugs, 15(3), 231-259. https://doi.org/10.2165/00023210-200115030-00008
Woelfer, M., Li, M., Colic, L., Liebe, T., Di, X., Biswal, B., ... & Walter, M. (2019). The role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Neuropsychopharmacology, 44(3), 525-536. https://doi.org/10.1038/s41386-018-0171-8
Reznikov, L. R., Grillo, C. A., Piroli, G. G., Pasumarthi, R. K., Reagan, L. P., & Fadel, J. (2007). Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment. European Journal of Neuroscience, 25(10), 3109-3114. https://doi.org/10.1111/j.1460-9568.2007.05560.x
Nobile, B., & Durand, M. (2015). Tianeptine: a controlled substance. Journal of Clinical Psychiatry, 76(11), e1478-e1479. https://doi.org/10.4088/JCP.15com10289
Park, S. W., Lee, C. H., Cho, H. Y., Seo, M. K., Lee, J. G., Lee, B. J., ... & Kim, Y. H. (2014). Effects of the atypical antidepressant tianeptine on the startle reflex and prepulse inhibition in the rat. Psychopharmacology, 231(16), 3169-3181. https://doi.org/10.1007/s00213-014-3503-4
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These articles investigate various aspects of tianeptine's pharmacology, its antidepressant-like activity, the relationship between depression and dementia, and the molecular mechanisms of neuroplasticity. Access to full-text articles might require a subscription or purchase from the respective publishers."
Outline tianeptine's effect on the glutamate receptors
Tianeptine's effects on glutamate receptors as follows:
Tianeptine is known to modulate the glutamatergic system, which plays a crucial role in its antidepressant and anxiolytic effects. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is involved in various brain functions, including learning, memory, and mood regulation.
Tianeptine's effects on glutamate receptors appear to be primarily through its modulation of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors. These receptors are critical for synaptic plasticity and neuronal communication.
AMPA receptor modulation: Tianeptine is known to enhance the function of AMPA receptors. It increases AMPA receptor trafficking to the cell membrane, which enhances the synaptic response to glutamate. This increased activity at the AMPA receptors may contribute to the neuroplasticity-enhancing effects of tianeptine and its ability to alleviate depressive symptoms.
NMDA receptor modulation: Tianeptine also has a modulatory effect on NMDA receptors. It has been suggested that tianeptine may attenuate the overactivation of NMDA receptors, which can occur during periods of stress or in certain neuropsychiatric disorders. By preventing excessive activation of NMDA receptors, tianeptine may help to protect neurons from excitotoxicity and promote a healthier balance of glutamatergic signaling.
Overall, tianeptine's actions on glutamate receptors play a significant role in its therapeutic effects. By modulating AMPA and NMDA receptor function, tianeptine can enhance neuroplasticity and promote resilience to stress, which may help alleviate depressive symptoms and anxiety."
What are tianeptine's effects on the dopamine system?
The effects of tianeptine on the dopamine system as follows:
Tianeptine's effects on the dopamine system are complex and not entirely understood. While tianeptine's primary mechanism of action involves modulation of glutamate receptors and the enhancement of neuroplasticity, it has been suggested that tianeptine may indirectly influence the dopamine system as well.
Research has shown that tianeptine may increase dopamine levels in specific brain areas, such as the nucleus accumbens and the prefrontal cortex. These brain regions are associated with reward, motivation, and cognitive functioning. The increase in dopamine levels in these areas may contribute to tianeptine's antidepressant and anxiolytic effects.
In addition, tianeptine has been shown to modulate dopamine D2 and D3 receptors, albeit with weak affinity. This interaction might contribute to the overall neurochemical effects of the drug. However, further research is needed to elucidate the precise role of tianeptine's influence on the dopamine system in its therapeutic actions.
It is important to note that tianeptine's effects on the dopamine system are not as pronounced as those of typical dopaminergic drugs, and its primary mechanism of action is distinct from that of dopaminergic antidepressants or psychostimulants."
Explain tianeptine's effect on cognition
"The effects of tianeptine on cognition as follows:
Tianeptine's impact on cognition is thought to be primarily due to its modulatory effects on the glutamatergic system, which plays a crucial role in various cognitive functions such as learning, memory, and attention.
Enhanced neuroplasticity: Tianeptine's ability to modulate AMPA and NMDA receptors in the brain contributes to enhanced neuroplasticity. Neuroplasticity is the capacity of the brain to reorganize and adapt in response to new experiences or stimuli, which is critical for learning and memory processes. By promoting neuroplasticity, tianeptine may have a positive effect on cognitive functioning.
Reduced cognitive impairment due to stress: Chronic stress can impair cognitive functions such as memory, attention, and decision-making. Tianeptine's anxiolytic and antidepressant effects can help alleviate stress, which may contribute to better cognitive performance in individuals experiencing stress-related cognitive impairment.
Neuroprotection: Tianeptine has been shown to have neuroprotective effects, as it can reduce neuronal damage caused by excitotoxicity and oxidative stress. By protecting neurons from damage, tianeptine may help maintain optimal cognitive function.
Improved mood and motivation: Tianeptine's antidepressant effects can lead to an improvement in mood and motivation, which can, in turn, positively influence cognitive performance. When individuals experience a reduction in depressive symptoms, they may be better able to concentrate, make decisions, and engage in learning activities.
It is important to note that the cognitive effects of tianeptine may vary among individuals and can be influenced by factors such as dose, duration of treatment, and the presence of any coexisting psychiatric or medical conditions. Further research is needed to better understand the full extent of tianeptine's impact on cognition and its potential as a cognitive enhancer."
What explains the feelings of serenity reported by some tianeptine users?
"The feelings of serenity reported by some tianeptine users can be attributed to several factors:
Anxiolytic effects: Tianeptine has been shown to possess anxiolytic properties, helping to reduce anxiety and promote a sense of calm. The modulation of glutamate receptors, particularly the inhibition of overactivation of NMDA receptors, may contribute to these anxiolytic effects. Additionally, tianeptine's indirect influence on the dopamine and serotonin systems may also play a role in reducing anxiety.
Antidepressant effects: Tianeptine's antidepressant effects can help alleviate symptoms of depression, such as persistent sadness, hopelessness, and irritability. As depressive symptoms are alleviated, users may experience an improved mood and a sense of well-being, which can contribute to feelings of serenity.
Stress resilience: Tianeptine has been shown to enhance stress resilience by modulating the stress response and promoting neuroplasticity. As a result, individuals taking tianeptine may be better equipped to handle stressors and maintain emotional stability, which could contribute to a sense of calm and serenity.
Individual variability: It is essential to consider that individual variability can play a significant role in the subjective experiences of tianeptine users. Factors such as genetics, baseline mental health, and the presence of co-occurring conditions may influence the extent to which individuals experience feelings of serenity while using tianeptine.
While tianeptine can help promote feelings of serenity in some users, it is important to remember that individual experiences may vary. It is always recommended to consult with a healthcare professional before starting, changing, or stopping any medication."
Why is tianeptine known in the USA as "gas station heroin"?
"The term "gas station heroin" is a colloquial nickname for tianeptine in the United States, which has emerged due to several factors:
Opioidergic properties: Tianeptine acts as a full agonist at the mu-opioid receptor, similar to opioids like morphine or heroin. Although its primary use is as an antidepressant, at higher doses, it can produce euphoria, analgesia, and other opioid-like effects.
Abuse potential: The euphoric effects of tianeptine at high doses can lead to misuse and addiction in some individuals. In the United States, where the opioid crisis has been a significant public health concern, the abuse potential of tianeptine has raised alarm.
Accessibility: Tianeptine is not approved by the FDA for use in the United States, and as a result, it is not available as a prescription medication. However, it has been sold over the counter as a dietary supplement in some establishments, such as gas stations, which has made it relatively easy to access for those seeking its opioid-like effects. This accessibility has contributed to its reputation as "gas station heroin."
Legal status: While not federally regulated in the United States, several states have recognized the potential for tianeptine abuse and have implemented regulatory measures to control its distribution and sale.
It is important to remember that tianeptine is a medication intended to treat depression and anxiety disorders when used appropriately and under the guidance of a healthcare professional. The nickname "gas station heroin" reflects the potential for misuse and abuse of the drug, rather than its intended therapeutic use."
Adverse side-effects of tianeptine can include euphoria. How can the euphoriant effect of high-dose tianeptine be mitigated?
"Σ: Mitigating the euphoriant effect of high-dose tianeptine involves a few important considerations:
Adhere to the prescribed dose: The best way to avoid the euphoriant effects of tianeptine is to follow the prescribed dosage regimen. Do not take higher doses than recommended by the healthcare provider, as this increases the risk of experiencing euphoria and other adverse effects.
Regular monitoring: Patients should have regular check-ups with their healthcare provider to assess their response to tianeptine and to adjust the dose if necessary. This helps to ensure that patients receive the most effective treatment while minimizing the risk of side effects.
Education: It is essential for patients and healthcare providers to be educated about the potential risks and side effects associated with tianeptine misuse, including its euphoriant effects. This can help patients understand the importance of adhering to the prescribed dose and the potential consequences of misuse.
Alternative treatment options: If the risk of euphoria or other adverse effects is a concern for a particular patient, healthcare providers may consider alternative antidepressant medications that have a lower risk of causing euphoria.
Please note that it is essential for individuals to consult with a healthcare professional before making any changes to their medication or dosage."

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