Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family.[2][3] It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a lesser extent as a norepinephrine reuptake inhibitor.[2][3]
Amineptine was developed by the French Society of Medical research in the 1960s.[4] Introduced in France in 1978 by the pharmaceutical company Servier,[5] amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, stimulant effect experienced by some patients.
After widespread adoption of this drug, cases of hepatotoxicity emerged, some serious.This, along with the potential for abuse, led to the suspension of the French marketing authorization for Survector in 1999.[6][7]
Amineptine is illegal in both Germany and the United States.
Medical uses
Amineptine was approved in France for severe clinical depression of endogenous origin in 1978.[8]
Contraindications
Chorea
Hypersensitivity: Known hypersensitivity to amineptine, in particular antecedents of hepatitis after dosage of the product.
MAO inhibitors
Precautions for use
Warnings and precautions before taking amineptine:[9]
Breast feeding
Children less than 15-year of age
General anaesthesia: Discontinue the drug 24 to 48 hours before anaesthesia.
Official sports/Olympic Games: Prohibited substance.
7 March Official Journal 2000.
Side effects
Dermatological
Severe acne due to amineptine was first reported in 1988 by various authors—Grupper, Thioly-Bensoussan, Vexiau, Fiet, Puissant, Gourmel, Teillac, Levigne, to name a few—simultaneously[10][11][12][13][14] in the same issue of Annales de Dermatologie et de Vénéréologie and in the 12 March 1988 issue of The Lancet.[15] A year later, Dr Martin-Ortega and colleagues in Barcelona, Spain reported a case of "acneiform eruption" in a 54-year-old woman whose intake of amineptine was described as "excessive."
Pharmacology
Pharmacodynamics
Amineptine inhibits the reuptake of dopamine and, to a much lesser extent, of norepinephrine.[37][34][40] In addition, it has been found to induce the release of dopamine.[37][34][40] However, amineptine is much less efficacious as a dopamine releasing agent
Society and culture
Brand names
Amineptine has been sold under a variety of brand names including Survector, Maneon, Directim, Neolior, Provector, and Viaspera.
Legal status
It had been proposed that Amineptine become a Schedule Icontrolled substance in the United States in July 2021.[44] This announcement was followed by the placement of Amineptine into Schedule I.[45]
Research
Wakefulness
Amineptine shows wakefulness-promoting effects in animals and might be useful in the treatment of narcolepsy.[46][47][48][49]
2.Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor Pharmacology, Biochemistry, and Behavior, June 1999^
3.The role of dopamine in the pathophysiology of depression Archives of General Psychiatry, March 2007^
One year after that, Vexiau and colleagues reported six women, one of whom never admitted to using amineptine, getting severe acne concentrated in the face, back and
(Accutane) for about 18 months; two of the three that discontinued amineptine experienced a reduction in cutaneous symptoms, with the least affected patient going into remission.
Psychomotor excitation can very rarely occur with this drug.
Insomnia
Irritability
Nervousness
Suicidal ideation. Seen early in the treatment, by lifting of psychomotor inhibition.
Abuse and dependence
The risk of addiction is low, but exists nonetheless.Between 1978 and 1988, there were 186 cases of amineptine addiction reported to the French Regional Centres of Pharmacovigilance; an analysis of 155 of those cases found that they were predominantly female, and that two-thirds of cases had known risk factors for addiction.[18] However, a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects.[19] In a 1990 study of eight amineptine dependence cases, the gradual withdrawal of amineptine could be achieved without problems in six people; in two others, anxiety, psychomotor agitation, and/or bulimia appeared.[20]
Withdrawal
Pharmacodependence is very common with amineptine compared to other antidepressants.[21] A variety of psychological symptoms can occur during withdrawal from amineptine,[22] such as anxiety and agitation.[23]
Abuse and dependence
The risk of addiction is low, but exists nonetheless.Between 1978 and 1988, there were 186 cases of amineptine addiction reported to the French Regional Centres of Pharmacovigilance; an analysis of 155 of those cases found that they were predominantly female, and that two-thirds of cases had known risk factors for addiction.[18] However, a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects.[19] In a 1990 study of eight amineptine dependence cases, the gradual withdrawal of amineptine could be achieved without problems in six people; in two others, anxiety, psychomotor agitation, and/or bulimia appeared.[20]
Withdrawal
Pharmacodependence is very common with amineptine compared to other antidepressants.[21] A variety of psychological symptoms can occur during withdrawal from amineptine,[22] such as anxiety and agitation.[23]
Cardiovascular
Very rarely:
Arterialhypotension
Palpitations
Vasomotor episode
Hepatic
Amineptine can rarely cause hepatitis, of the cytolytic, cholestatic varieties.[24] Amineptine-induced hepatitis, which is sometimes preceded by a rash, is believed to be due to an immunoallergic reaction.[25] It resolves upon discontinuation of the offending drug.[24] The risk of getting this may or may not be genetically determined.[26]
Additionally, amineptine is known to rarely elevate transaminases, alkaline phosphatase, and bilirubin.[27]
Mixed hepatitis, which is very rare, generally occurs between the 15th and 30th day of treatment of amineptine. Often preceded by sometimes intense abdominal pains, nausea, vomiting or a rash, the jaundice is variable. Hepatitis is either of mixed type or with cholestatic prevalence. The evolution was, in all the cases, favorable to the discontinuation of the drug. The mechanism is discussed (immunoallergic and/or toxic).[28]
In circa 1994 Spain, there was a case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment.[29]
Lazaros and colleagues at the Western Attica General Hospital in Athens, Greece reported two cases of drug induced hepatitis 18 and 15 days of treatment.[30]
One case of cytolytic hepatitis occurred after ingestion of only one tablet.[31]
Gastrointestinal
Acute pancreatitis (very rare) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment.[29]
Immunological
A case of anaphylactic shock in a woman who had been taking amineptine has been reported.[32]
No human data appear to be available for binding or inhibition of the monoamine transporters by amineptine.[41]
Pharmacokinetics
Peak plasma levels of amineptine following a single 100 mg oral dose have been found to range between 277 and 2,215 ng/mL (818–6,544 nM), with a mean of 772 ng/mL (2,281 nM), whereas maximal plasma concentrations of its major metabolite ranged between 144 and 1,068 ng/mL (465–3,452 nM), with a mean of 471 ng/mL (1,522 nM).[42] After a single 200 mg oral dose of amineptine, mean peak plasma levels of amineptine were around 750 to 940 ng/mL (2,216–2,777 nM), while those of its major metabolite were about 750 to 970 ng/mL (2,216–3,135 nM).[43] The time to peak concentrations is about 1 hour for amineptine and 1.5 hours for its major metabolite.[42][43] The elimination half-life of amineptine is about 0.80 to 1.0 hours and that of its major metabolite is about 1.5 to 2.5 hours.[42][43] Due to their very short elimination half-lives, amineptine and its major metabolite do not accumulate significantly with repeated administration.[42]
6.Docket No. 02N-0101 U.S. Food and Drug Administration, 2002-04-09, retrieved 2014-01-30^
7.{{UN document |docid=E/CN.7/2003/12 |body=E |session=46 |title=Implementation of the international drug control treaties: changes in the scope of control of substances |access-date=2026-03-31 |date=2003-04-17}}^
10.[New iatrogenic acne: acne caused by amineptin (Survector)] Annales de Dermatologie et de Venereologie, 1988^
11.[Iatrogenic acne caused by amineptin (Survector). Apropos of 8 cases] Annales de Dermatologie et de Venereologie, 1988^
12.[Severe lesions of acne type induced by chronic amineptin poisoning: apropos of 6 cases] Annales de Dermatologie et de Venereologie, 1988^
13.[Acne caused by Survector] Annales de Dermatologie et de Venereologie, 1988^
14.[Monstrous acne in the adult. Inducer role of Survector?] Annales de Dermatologie et de Venereologie, 1988^
15.Severe acne-like lesions caused by amineptine overdose Lancet, March 1988^
16.[Acneiform eruption induced by amineptin (Survector)] Medicina Cutanea Ibero-Latino-Americana, 1989^
17.Severe acne due to chronic amineptine overdose Archives of Dermatological Research, 1990^
18.[Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance] Therapie, 1990^
19.[Amineptine and amotival syndrome (author's transl)] L'Encephale, 1981^
20.[Amineptin dependence. Detection of patients at risk. Report of 8 cases] L'Encephale, 1990^
21.[Pharmacovigilance of new antidepressants: evaluation of neuro-psychobehavioral disorders] Therapie, 1997^
22.[Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance] Therapie, 1990^
23.[Amineptin dependence. Detection of patients at risk. Report of 8 cases] L'Encephale, 1990^
24.[Amineptine-induced cholestatic hepatitis. 5 cases (author's transl)] La Nouvelle Presse Médicale, December 1980^
25.Acute and chronic drug-induced hepatitis Bailliere's Clinical Gastroenterology, April 1988^
26.Genetic predisposition to drug-induced hepatotoxicity Journal of Hepatology, 1997^
29.Hepatic and pancreatic injury associated with amineptine therapy Journal of Clinical Gastroenterology, March 1994^
30.Amineptine induced liver injury. Report of two cases and brief review of the literature Hepato-Gastroenterology, 1996^
31.[Immediate acute hepatic cytolysis after the administration of a single amineptin tablet] Gastroenterologie Clinique et Biologique, 1992^
32.[Anaphylactic shock caused by amineptine. Report of a case] La Revue de Médecine Interne, 1989^
33.PDSP Ki Database Psychoactive Drug Screening Program (PDSP), University of North Carolina at Chapel Hill and the United States National Institute of Mental Health, retrieved 14 August 2017^
34.Pharmacology of amineptine: synthesis and updating Clinical Neuropharmacology, 1989^
35.Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants Sleep Research Online, 1998^
36.Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes Journal of Natural Products, October 1995^
37.Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain British Journal of Pharmacology, May 1986^
38.Acute effects of atypical antidepressants on various receptors in the rat brain Acta Pharmacologica et Toxicologica, May 1984^
39.Effects of antidepressant drugs on histamine-H1 receptors in the brain Life Sciences, February 1984^
40.Pharmacology of amineptine, an antidepressant agent acting on the dopaminergic system: a review International Clinical Psychopharmacology, July 1997^
41.Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters Chemical Communications, July 2009^
42.Single-dose pharmacokinetics of amineptine and of its main metabolite in healthy young adults Fundamental & Clinical Pharmacology, 1989^
43.Pharmacokinetics of amineptine in man European Journal of Drug Metabolism and Pharmacokinetics, 1981^
