Biology and Chemistry of Tianeptine
Atypical Tricyclic Antidepressant
An Explanation of the Chemistry
Conventional tricyclic antidepressants (TCAs) work by obstructing the reuptake of neurotransmitters that regulate temperament and pain. They moderate the levels of re-absorbed serotonin, norepinephrine, and dopamine, which is essential in the clinical reduction of depression and anxiety (Moraczewski et al., 2023). However, typical TCAs have, over time, seen limited use in clinical settings due to their low threshold for overdose. They inhibit acetylcholine, which is essential in the proper functioning of the parasympathetic nerves that regulate involuntary motion in the respiratory and gastrointestinal organs.
Notably, tianeptine has a biochemical structure resembling that of TCAs (Smith et al., 2023). However, its action is completely different because it decreases serotonin transmission by illogically increasing its presynaptic uptake (Galust et al., 2023). This paradox is further explored by Edinoff et al. (2023), who point out that first-line treatments for depression, serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake by impeding the functioning of the neurotransmitter’s transport agent. Tianeptine atypically promotes serotonin uptake, according to certain neurological experts.
Biological and Pharmacological Applications
Tianeptine’s atypical TCA status is entirely counterintuitive to its use as an antidepressant and has been widely questioned in certain corners of the neuro-psychiatry world. Wagner et al. (2023) suggest that the description of tianeptine as an “atypical TCA” is entirely erroneous and that it has no affinity or effect on serotonin production or its transmission. In agreement with Lauhan et al. (2018), they argue that its anti-depressive properties are owed to its ability to induce neuroplastic alterations in parts of the brain concerned with mood regulation.
Further, Wagner et al. (2023) credit tianeptine with questioning the long-held belief that depression is solely caused by an imbalance in neurotransmitter concentrations. Edinoff et al. (2023) offer an alternative explanation by claiming that tianeptine primarily regulates depression through its ability to modulate glutamate. However, there is consensus that tianeptine is effective as an antidepressant, which is marketed under brand names such as Stablon and Tatinol in more than 60 nations (Galust, 2023). It is typically prescribed clinically at doses of 12.5-50mg per day, depending on a patient’s presentation. It is from this original use that it has proliferated and gained infamy as a mood-enhancing drug.
Opioid Agonist Properties
An Explanation of the Chemistry
At extremely high doses compared to the therapeutic thresholds, tianeptine acts as an opioid agonist. Wagner et al. (2023) highlight its capacity to cause agonism in the µ-opioid receptor and δ-receptors of the brain. In perspective, heroin and oxycodone are termed full opioid agonists in that they produce short-term feelings of euphoria and elation. Similar to outlawed opioids, tianeptine has a high potential for abuse among people seeking a dopamine rush.
Additionally, µ-opioid receptor agonism is typically accompanied by a stimulation of the glutamatergic mechanism, leading to an elevation of tianeptine’s anti-depressive actions in the user (Edinoff et al.,2023). Its direct opposite is naloxone, which is commonly administered in overdose cases (Lauhan et al., 2018). Thus, its use as a stimulant is well established, leading to its abuse and calls for its scheduling by the FDA from certain quarters.
Biological Implications
Tianeptine can, therefore, become very popular among people with prior opioid addiction or users of illegal drugs such as heroin currently seeking to avoid problems with the law. However, it has a relatively short pharma-kinetic half-life of two and a half hours, whereby it is quickly absorbed once inside the user’s gastrointestinal tract (Edinoff et al., 2023). The dosage used by people with dependence is usually very high and requires periodic upscaling due to tolerance build-up.
Lauhan et al. (2018) report a case of a patient with three and a half times the usual dosage. Smith et al. (2023) point out dose escalations by more than 1000 times therapeutic recommendations by persons initially taking prescribed quantities. Casual users have periods of debilitating withdrawal symptoms between doses that necessitate larger intake quantities at less spaced intervals.
The Biology of Tianeptine: Toxicity
From the preceding sections, tianeptine users usually develop opioid toxicity. There is no evidence of toxicity similar to that of TCAs despite them sharing a similar structure (Galust, 2023). Wagner et al. (2023) point out that out of 114 reported cases of tianeptine toxicity, 48% were neurological, a third were cardiovascular, and 24% were gastrointestinal-related complaints.
Roughly a quarter of the reported cases were hospitalized in an intensive care unit. There were no deaths in documented cases between 2000 and 2017. This is due to the efficacious use of naloxone to reverse the effects of tianeptine, even in the most severe cases. Smith et al. (2021) point out that intravenous intake of the drug can result in damaged tissues and hepatic toxicity. This mode of intake is rarely used by users who typically ingest pills orally.
Commercial Exploitation of Tianeptine in the USA
Pharmacological Exploitation as an Antidepressant
The potential commercial use of tianeptine as an antidepressant in the USA is self-evident. Beeder and Samplaski(2019) note that 110 out of 1000 people in the USA are on prescription antidepressants. However, Smith et al. (2023) observe that the FDA has never placed tianeptine under any approval program because the costs of a clinical trial for the drug outweigh the benefits.
In line with this statement, Johnson and Johnson, a pharmaceutical company, carried out a single-phase clinical trial 14 years ago before abandoning it completely. Seale et al. (2023) argue that its potential for severe addiction and opioid qualities rule it out as a prescription medication. It, therefore, remains to be seen whether tianeptine’s anti-depressive properties will be commercially exploited.
Commercial Exploitation as a “Gas Station Heroin”
As stated earlier, tianeptine is commonly sold over the counter in small-scale retail stores and thus qualifies for the category of retail substances termed “gas station drugs.” Today, these drugs are most commonly sold over the Internet, whereby customers place orders and have them delivered. Edinoff et al. (2023) posit that they are commercially and industrially produced to mimic more popular but illegal drugs. The people who own the laboratories that churn these drugs out do it clandestinely as they are not a mainstream enterprise. A more well-known example of this class of drugs is spice, a presently banned synthetic form of marijuana.
Marketing
Market Penetration
To confound buyers, manufacturers normally misrepresent their product as having desirable utility. Therefore, it can be inferred that a deliberate market penetration strategy of the drug manufacturers involves getting as many people hooked to their product as possible. An example is Tianaa, a trademarked brand of tianeptine-based products in the USA. In this case, the specific market being penetrated is people susceptible to opioid addiction.
Seale et al. (2023) note that it is commonly sold as a dietary supplement trademarked in the USA as Tianaa. The product has three brands in the form of pills colored green, white, and red, each with a different advertised effect, including”calming,” “stimulating,” and “hallucinogenic.” Each brand contains tianeptine in combination with other substances to achieve the advertised states. In their investigative study of Tianaa, Seale et al. (2023) find that pills, including those of the same brand, have a variable quantity of tianeptine.
In other cases, tianeptine is marketed as producing commonly sought-after states of mind. Some marketers present it as a sexual performance booster, a mood elevator, and a cognitive enhancer (Edinoff et al., 2023). In some cases, it is advertised as assistive for persons undergoing opioid withdrawal or for whom painkillers have ceased to be effective or prescribed.
However, such people end up ditching an old addiction and acquiring a new one to a legal drug. Over time, they become dedicated customers of a particular brand of tianeptine. Thus, its marketing strategy is primarily focused on deceiving the customer through false advertising, only to entrap them through a costly but legal addiction.
Market Segmentation
A visit to a popular online site where people can order tianeptine products reveals several brands of the product. They include “ZA ZA,” “PEGASUS,” and “TD RED,” sold on Burmans Health Shop online (Burman Health Shop, 2023). The colorful pill bottles are advertised as dietary supplements ranging from $35 to $50. There are user reviews indicating the effectiveness of the products as advertised.
Thus, the sellers of the popular brands are targeting an online market in addition to selling physically in bodegas, gas station shops, and smoke shops. For physical sales, the drug is widely used by people who already use other drugs and are buying it to diversify their drug use or because they cannot access prohibited opioids (Wagner et al., 2023). Data on sales volume and buyer statistics cannot be accessed as the manufacturers are not mainstream and do not share their business information.
Product Differentiation Between Brands
To counteract its quick half-life, consumers and manufacturers are devising increasingly creative ways to ingest the drug. Instead of the usual hard gelatin capsule, a star-shaped polyester-based capsule is being marketed and sold to people with an addiction online that promises a delayed release and a prolonged high Galust et al., (2023). The capsule material is caprolactone, which facilitates long-term content release before eventual dissolution.
Moreover, each arm of the star-shaped creation accommodates 15mg of tianeptine, which means one can take a higher dose in one go as opposed to swallowing multiple pills. This novel approach to tianeptine intake may be the new way it is being marketed to circumvent having a brief high. It is evidence that manufacturers are undertaking product development in order to meet the needs of their customers and differentiate their products from competitors’ offerings.
Conclusion
The pharmacological profile of tianeptine, an unusual tricyclic antidepressant, is paradoxical as it combines antidepressant effects with opioid agonist actions. Consequently, its use in the medical and recreational spheres remains controversial. Through understanding the biological aspects and chemistry of tianeptine, its potential application, as well as risks, can be realized. Moreover, tianeptine challenges traditional theories of depression being caused by neurotransmitter imbalances, among other factors; the drug does not inhibit neurotransmitter reuptake like conventional TCAs but instead increases presynaptic uptake of serotonin. It is, therefore, considered a very effective antidepressant used in more than 60 countries worldwide.
On the downside, though, this substance has opioid agonist properties that come to light when one looks into it carefully. At high doses, it acts on µ-opioid receptors much like classical opioids, thereby causing euphoric feelings. The biological implications of tianeptine’s use underlie its potential attractiveness to a subject with a history of opioid addiction.
Due to its short half-life, patients must take repeated higher doses for long-lasting effects, leading to tolerance and withdrawal problems. These were extreme overdose cases resulting in tissue damage. Nonetheless, although less toxic than traditional TCAs, tianeptine has been associated with significant numbers of reports of neurological, cardiovascular, and gastrointestinal complaints, including death.
There is a potential market for these drugs in the US, where there are high rates of antidepressant use in the population. Nevertheless, a lack of approval by the FDA, together with its suspected risk for addiction and opiate-like properties, gives rise to ethical and regulatory issues. Tianeptine’s entry into the world of “gas station drugs” has been accomplished through many brands that deceive consumers by false advertising. On the other hand, the online market is oriented towards different groups of people due to colorful pill bottles and advertised effects. The legal alternatives to opioids are exploited by firms that manufacture these drugs in different forms, such as star-shaped capsules, to make them distinct and prolong their duration.
The dual nature of tianeptine as an antidepressant with opioid agonist properties reflects the complex interplay between its chemical structure and biological effects. This raises the issue of whether it should be commercial exploitation concerning tianeptine both for legitimate uses as an antidepressant or a “gas station heroin,” thereby posing ethical, medical, and regulatory questions. However, this discussion continues about finding a balance between potential therapeutic benefits versus abuse risks, which is crucial for both regulation commissioners and the scientific community.
References
Beeder, L. A., & Samplaski, M. K. (2019). Effect of antidepressant medications on semen parameters and male fertility. International Journal of Urology, 27(1), 39–46. Web.
Burmans Health Shop. (2023). ZAZA RED (TIANEPTINE). Burman’s Health Shop. Web.
Edinoff, A. N., Sall, S., Beckman, S. P., Koepnick, A. D., Gold, L., Jackson, E. D., Wenger, D. M., Cornett, E. M., Murnane, K. S., Kaye, A. M., & Kaye, A. D. (2023). Tianeptine, an antidepressant with opioid agonist effects: Pharmacology and abuse potential, a narrative review. Pain and Therapy, 12(5), 1121–1134. Web.
Galust, H., Seltzer, J., Hardin, J., Friedman, N. B., & Minns, A. B. (2023). “Tianeptine abuse via novel, extended-release, star-shaped, drug delivery device.” Toxicology Reports, 11, 162–164. Web.
Lauhan, R., Hsu, A., Alam, A., & Beizai, K. (2018). Tianeptine abuse and dependence: Case report and literature review. Psychosomatics, 59(6), 547–553. Web.
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Seale, J. T., Garden, E. A., French, J. K., & McDougal, O. M. (2023). Analysis of tianeptine in dietary supplements. Nutraceuticals, 3(3), 481–488. Web.
Smith, K. E., Rogers, J. M., Strickland, J. C., & Epstein, D. H. (2021). When an obscurity becomes trend: Social-media descriptions of tianeptine use and associated atypical drug use. The American Journal of Drug and Alcohol Abuse, 47(4), 1–12. Web.
Wagner, M., Pergolizzi, J. V., Jo Ann LeQuang, Breve, F., & Giustino Varrassi. (2023). From antidepressant tianeptine to street drug “ZaZa”: A narrative review. Cureus, 15(6). Web.