AMINEPTINE

'Amineptine' (trade names 'Maneon' [Italy], 'Survector' [Spain, Italy, Philippines]) is an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine^[1] and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect.
Introduced in France in 1978 by the pharmaceutical giant Servier Pharmaceutical Manufacturing Encyclopedia, , Marshall, Sittig, William Andrew Publishing/Noyes Publications, , ISBN 0-8155-1144-2 and marketed under the trade name 'Survector', amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, stimulant effect experienced by some patients. (This is to be distinguished from its antidepressant effect, which appears in approximately 7 days after commencing treatment.) This led to the Food and Drug Administration suspending the marketing authorisation for Survector in 1999 and France withdrew it from the market, however several developing countries continued to produce it up until 2005.
Currently amineptine is off-patent and very difficult to obtain. Rare cases of hepatotoxicity, some serious, have been reported, but these were thought to be due to a genetic predisposition.

Therapeutic indications

Approved

Amineptine was approved in France for severe clinical depression of endogenous origin in 1978. SURVECTOR - Amineptine Doctissimo

Unapproved/Off-Label/Investigational

Parkinson's Disease, amotivational syndromes, ADHD (Attention Deficit/Hyperactivity Disorder)

Mechanism of action

★ Inhibitor of the reuptake of norepinephrine and dopamine.

★ Little anticholinergic or antihistaminic effects.

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{{cite journal | author=Grupper C | title=[New iatrogenic acne: acne caused by amineptin (Survector)] | journal=Annales de Dermatologie et de Venereologie | volume=115 | issue=11 | year=1988 | pages=1174-6 | id= [Article in French] List of Library Holdings Worldwide{{cite journal | author=Thioly-Bensoussan D, Charpentier A, Triller R, Thioly F, Blanchet P, Tricoire N, Noury JY, Grupper C | title=[Iatrogenic acne caused by amineptin (Survector). Apropos of 8 cases] | journal=Annales de Dermatologie et de Venereologie | volume=115 | issue=11 | year=1988 | pages=1177-80 | id= [Article in French] List of Library Holdings Worldwide{{cite journal | author=Vexiau P, Gourmel B, Husson C, Castot A, Rybojad M, Julien R, Fiet J, Puissant A, Cathelineau G | title=[Severe lesions of acne type induced by chronic amineptin poisoning: apropos of 6 cases] | journal=Annales de Dermatologie et de Venereologie | volume=115 | issue=11 | year=1988 | pages=1180-2| id= [Article in French] List of Library Holdings Worldwide{{cite journal | author=Teillac D, Weber MJ, Lowenstein W, de Prost Y | title=[Acne caused by Survector] | journal=Annales de Dermatologie et de Venereologie | volume=115 | issue=11 | year=1988 | pages=1183-4 | id= [Article in French] List of Library Holdings Worldwide{{cite journal | author=Levigne V, Faisant M, Mourier C, Garcier F, Millon-Paitel M, Barthelemy H, Claudy A | title=[Monstrous acne in the adult. Inducer role of Survector?] | Journal=journal=Annales de Dermatologie et de Venereologie | volume=115 | issue=11 | year=1988 | pages=1184-5 | id= [Article in French] List of Library Holdings Worldwide in the same issue of ''Annales de Dermatologie et de Venereologie'' and in the 12 March 1988 of ''The Lancet.''{{cite journal | author=Vexiau P, Gourmel B, Julien R, Husson C, Fiet J, Puissant A, Dreux C, Cathelineau G | title=Severe acne-like lesions caused by amineptine overdose | journal=Lancet | volume=1 | issue=8585 | year=1988 | pages=585 | id= List of Library Holdings Worldwide 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."{{cite journal | author=Martin-Ortega E, Zamora E, Herrero C, Palou J | title=[Acneiform eruption induced by amineptin (Survector)] | journal=Medicina Cutanea Ibero-Latino-Americana | volume=17 | issue=6 | year=1989 | pages=414-6 | id= [Article in Spanish] List of Library Holdings Worldwide 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 thorax, the severity of which varied with the dosage.{{cite journal | author=Vexiau P, Gourmel B, Castot A, Husson C, Rybojad M, Julien R, Fiet J, Hardy N, Puissant A, Cathelineau G | title=Severe acne due to chronic amineptine overdose | journal= Archives of Dermatological Research | volume=282 | issue=2 | year=1990 | pages=103-7 | id= List of Library Holdings Worldwide Most of them were treated unsuccessfully with isotretinoin (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.
This can be seen as a general side effect of central dopamine enhancement, due to the inhibitory effect of dopamine on prolactine, with the subsequent increase in testosterone output, leading in turn to the same potential for acne as is typical of pubescents.

Psychiatric

Psychomotor excitation can very rarely occur with this drug. AMINEPTINE CHLORHYDRATE

★ Nervousness (very rare)

★ Irritability (very rare)

★ Insomnia (very rare)

★ Suicidal ideation (very rare) Seen in beginning of treatment. By lifting of psychomotor inhibition. Increase monitoring at the beginning of treatment.

Cardiovascular

★ Vasomotor episode (very rare)

★ Arterial hypotension (very rare)

★ Palpitations (very rare)

Hepatic

Amineptine can very rarely cause hepatitis, of the cytolytic, cholestatic varieties.{{cite journal | author=Bories P, Pomier-Layrargues G, Chotard JP, Citron D, Capron-Chivrac D, Capron JP, Michel H. | title=[Amineptine-induced cholestatic hepatitis. 5 cases (author's transl)] | journal= La Nouvelle Presse Medicale | volume=9 | issue=48 | year=1980 | pages=3689-92 | id= [Article in French] List of Library Holdings Worldwide Amineptine-induced hepatitis, which is sometimes preceded by a rash, is believed to be due to an allergic reaction.{{cite journal | author=Pessayre D, Larrey D. | title=Acute and chronic drug-induced hepatitis. | journal=Bailliere's Clinical Gastroenterology | volume=2 | issue=2 | year=1988 | pages=385-422 | id= List of Library Holdings Worldwide It resolves upon discontinuation of the offending drug. The risk of getting this may or may not be genetically determined. List of Library Holdings Worldwide
Additionally, amineptine is known to rarely elevate transaminases, alkaline phosphatase, and bilirubin. [Article in French] List of Library Holdings Worldwide
Mixed hepatitis, which is very rare, generally occurs between the 15th and 30th day of treatment. 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).

★
★ Concours Med 1982; 104:5733-5734.
In circa 1994 Spain, there was a case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment.{{cite journal | first = J. J. | last = Sebastian Domingo | coauthors = M. A. Simon Marco and R. Uribarrena Echebarria | year = 1994 | month = March | title = Hepatic and pancreatic injury associated with amineptine therapy | journal = Journal of Clinical Gastroenterology | volume = 18 | issue = 2 | pages = 168-9 | id=
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.{{cite journal | first = GA | last = Lazaros | coauthors = Stavrinos C, Papatheodoridis GV, Delladetsima JK, Toliopoulos A, Tassopoulos NC | year = 1996 | month = July-August | title = Amineptine induced liver injury. Report of two cases and brief review of the literature. | journal = Hepato-gastroenterology | volume = 43 | issue = 10 | pages = 1015-9 | id =
One case of cytolytic hepatitis occurred after ingestion of only one tablet.{{cite journal | first = AP | last = Jonville | coauthors = Dutertre JP, Autret E | year = 1992 | title = [Immediate acute hepatic cytolysis after the administration of a single amineptin tablet] | journal = Gastroenterologie clinique et biologique | volume = 16 | issue = 4 | pages = 368 | id =

Gastrointestinal

★ Acute pancreatitis (very rare) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment.

Immunological

In 1989, Sgro and colleagues at the Centre de Pharmacovigilance in Dijon reported a case of anaphylactic shock in a woman who had been taking amineptine.{{cite journal | author=Sgro C, Lacroix S, Waldner A, Lacroix M, Ferrut O, Bureau A. | title=[Anaphylactic shock caused by amineptine. Report of a case] | journal=La Revue de Medecine Interne | volume=10 | issue=5 | month=Sep-Oct | year=1989 | pages=461-2 | id= List of Library Holdings Worldwide

Effects on the unborn child

★ Non-teratogenic in animals

★ Lacking information in humans

Abuse and Dependence

The risk of addiction is low, but it is there 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.{{cite journal | author=Castot A, Benzaken C, Wagniart F, Efthymiou ML | title=[Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance] | journal=Therapie | volume=45 | issue=5 | year=1990 | pages=399-405 | id= [Article in French] List of Library Holdings Worldwide However, a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects.{{cite journal | author=Deniker P, Loo H, Zarifian E, Peron P, Benyacoub A, Roux JM, Kamoun A | title=[Amineptine and amotival syndrome (author's transl)] | journal=L'Encephale | volume=7 | issue=1 | year=1981 | pages=59-64 | id= [Article in French] List of Library Holdings Worldwide 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.{{cite journal | author=Bertschy G, Luxembourger I, Bizouard P, Vandel S, Allers G, Volmat R | title=[Amineptin dependence. Detection of patients at risk. Report of 8 cases] | journal=L'Encephale | volume=16 | issue=5 | year=1990 | pages=405-9 | id= [Article in French] List of Library Holdings Worldwide

Precautions for use

★ General anaesthesia: Discontinue the drug 24 to 48 hours before anaesthesia.

★ Pregnancy (first trimester)

★ Breast feeding

★ Official sports/Olympic Games: Prohibited substance.

★
★ 7 March Official Journal 2000.

Contraindications

★ Chorea

★ MAO inhibitors

★ Children less than 1 year of age

★ Hypersensitivity: Known hypersensitivity to amineptine, in particular antecedents of hepatitis after dosage of the product.

References

1. Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor, Vaugeois JM, Corera AT, Deslandes A, Costentin J, , , Pharmacol. Biochem. Behav., 1999

External links

★ Amineptine.com

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