Amineptine is an old antidepressant drug that was marketed for the treatment of major depression.
Its stimulating effects and addictive potential led the authorities to ban its sale and consumption twenty years ago. Today, this medicine is no longer used and is included in the list of controlled substances.
In this article we explain what amineptine is and what are the main characteristics of the group of antidepressants it belongs to , what is its mechanism of action, and what kind of side effects it produces.
What is amineptine?
Amineptine is an atypical antidepressant from the group of tricyclic antidepressants . It was developed and introduced to the market by the French company Servier in the 1970s to treat severe clinical depression of endogenous origin. After its launch it acquired a certain popularity because, apart from the effects of an antidepressant drug, it also produced exciting effects, short in duration but very pleasant, according to what the patients themselves experienced.
The stimulating effects of this drug led many people to make recreational use of it; moreover, after its marketing spread to several European countries, numerous cases of hepatotoxicity from misuse arose, some of them of considerable severity, which led the authorities to suspend the authorisation for its sale.
In 1999 the marketing of amineptine was banned in Spain , sold under the name of Survector, a measure that was extended to several European countries. However, the Food and Drug Administration (FDA) of the United States, a key institution at the global level when it comes to allowing certain drugs to be marketed or not, never approved amineptine for sale in its country.
Amineptine (in its hydrochloride form) is currently included in UN List II of controlled and monitored substances.
Amineptine belongs to the group of tricyclic antidepressants. This type of drug was discovered in the 1950s and, for a few decades, has been the first choice in the pharmacological treatment of clinical depression. Although they are still used for mood disorders (along with MAOIs or lithium, for example), they have now been replaced by another group of antidepressants.
Tricyclic antidepressants share some chemical characteristics with phenothiazines, a group of antipsychotic (or neuroleptic) medications used to relieve psychotic symptoms and suffering in emotional disturbances and severe mental disorders, despite their marked side effects.
It is precisely because of the many side effects that tricyclic antidepressants cause that today prefers to use other types of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs), two groups of antidepressants that generate fewer, milder adverse reactions.
Mechanism of action
Amineptine exerts its effects through inhibition of dopamine reuptake and, to a lesser extent, of noradrenaline. One of the peculiarities of the drug is that it also induces the release of dopamine, which explains its stimulant effects; however, the discharge of dopamine is relatively mild compared to other excitatory drugs, such as amphetamine, since its predominant effect seems to be the inhibition of the reuptake of this neurotransmitter, rather than its release.
Unlike dopamine, amineptine does not cause the release of noradrenaline and therefore acts only as a reuptake inhibitor. Tricyclic antidepressants usually interact with serotonin, adrenergic, dopamine, histamine, and acetylcholine (the muscarinic type) receptors; however, this doesn’t happen with amineptine, because the interaction is very weak or virtually nonexistent.
Amineptine shares some of the side effects of tricyclic antidepressants (such as insomnia or irritability) and, given its particular pharmacological profile, also causes organic complications and adverse reactions of its own, which are detailed below.
1. Dermatological problems
Cases of severe acne have been reported in people who have taken amineptine excessively. Specifically, we described the case of a 54-year-old woman whose excessive use of this drug caused an acneiform rash, characterized by the appearance of papules and pustules in seborrheic areas.
Several cases have also been described of women who, after continued consumption of amineptine, suffered severe acne on the face, back and chest, the severity of which varied with the dose.
2. Psychiatric disorders
Another of the side effects that amineptine consumption can produce is psychomotor excitation, although its appearance is very infrequent. This includes: insomnia, irritability, nervousness and suicidal ideation.
3. Potential for abuse and dependency
Although the risk of addiction is low, several cases of amineptine dependence were reported in several centres in France. In a study of 155 addicted people it was observed that they were predominantly women, and that two thirds of them had known risk factors for addiction.
However, research conducted in the 1980s with opiate addicts and schizophrenic patients found no amineptine addiction in any of the subjects. Another study, which looked at eight cases of amineptin dependence, found that gradual withdrawal of the drug was achieved without problems in six of the people, and symptoms of anxiety, psychomotor agitation and bulimia were observed in the other two.
4. Liver complications
Amineptine can rarely cause hepatitis (cytolytic and cholestatic). It has been suggested that the hepatitis induced by this drug, which is sometimes preceded by a rash, may be due to an allergic reaction and resolves by stopping the drug. In addition, amineptine is known not to raise transaminases, alkaline phosphatase, and bilirubin.
Mixed hepatitis, which is very rare, usually occurs within 15 to 30 days of treatment with this antidepressant. It is often preceded by abdominal pain (sometimes severe), nausea, vomiting, rash, and jaundice (variable). The course of the condition is usually favorable if amineptine treatment is discontinued.
In Spain, a case was identified in the mid-1990s in which acute pancreatitis and mixed hepatitis were associated, after three weeks of treatment with the drug.
5. Cardiovascular problems
Although it occurs rarely, after the consumption of amineptine, arterial hypotension, palpitations (hard, fast and/or irregular beats) and vasomotor or syncopal episodes (which occur with the transitory loss of consciousness, with spontaneous recovery and without sequelae) may occur.
Domingo, J. S., Marco, M. S., & Echebaría, R. U. (1994). Hepatic and pancreatic injury associated with amineptine therapy. Journal of clinical gastroenterology, 18(2), 168.
Garattini, S., & Mennini, T. (1989). Farmacología de la amineptina: síntesis y actualización. Neurofarmacología clínica, 12, S13-8.
Vaugeois, J. M., Corera, A. T., Deslandes, A., & Costentin, J. (1999). Aunque está químicamente relacionado con la amineptina, el antidepresivo tianeptina no es un inhibidor de la recaptación de dopamina. Pharmacology Biochemistry and Behavior, 63(2), 285-290.