Amineptine is an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect. Developed in France in 1978 by the pharmaceutical giant Servier and marketed under the trade name Survector®, amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, psychostimulant 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 FDA 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. For example, first degree relatives of patients who suffered hepatotoxicity also experienced the same phenomena.

Pharmacological properties 1. PSYCHOSTIMULANT ( principal some ) 2. ANTIDEPRESSANT ( principal some ) 3. NOOTROPIC ( to be confirmed )

Mechanism of action 1. Principal Probably identical to the tricyclic antidepressants. Inhibitor of the reuptake of noradrenalin and dopamine. Little anticholinergic or antihistaminic effects.

 Primary effects 

1. ANTIDEPRESSANT (principal)

 Therapeutic indications 

1. DEPRESSION (principal) of endogenous origin, reactionary or neurotic.

 Side effects 

1. ACNE (SOME) Monstrous iatrogenic form. The gravity of the lesions seems proportional to the amount. Treatment by isotretinoin: - Ann Dermatol Venereol 1988; 115:1177-1179. Severe cases of acne, following the use of large amounts, nine other cases were already reported: - J Dermatol Treat 1994; 5:143-144. A case in a 54 year old woman surdosée: - Int J Dermatol 1996; 35:892-893.

2. DRUG-ADDICTION (SOME) - To prescribe 1990; 10:199. - Therapie 1990; 45:51.

3. VASOMOTOR EPISODE (VERY RARE )

4. ARTERIAL HYPOTENSION (VERY RARE )

5. PALPITATIONS (VERY RARE )

6. NAUSEA (VERY RARE) can precede onset of hepatitis.

7. EPIGASTRIC PAIN (VERY RARE) can precede onset of hepatitis.

8. ABDOMINAL PAIN (VERY RARE) can precede onset of hepatitis.

9. RASH (VERY RARE) within the framework of a hepatic attack. Can precede jaundice by 24 to 48 hours.

10. TOXIC HEPATITIS (VERY RARE) Generally moderate and transitory increase in the hepatic enzymes. Several cases of hepatitis were reported. Their evolution was always favorable to the discontinuation of the drug: - Press Med 1980; 9:3689-3692. - Sem Hop Paris 1981; 57:1992-1996. Two additional cases: - Hepatogastroenterology 1996; 43-1015-1019.

11. ELEVATED TRANSAMINASES (RARE) Generally moderated, isolated and transitory increase.

12. ELEVATED ALKALINE PHOSPHATASE (RARE )

13. ELEVATED BILIRUBIN (RARE )

14. JAUNDICE (VERY RARE) Preceded by a pre-jaundice phase (abdominal pains, nausea, fever and rash), in which case the drug must be discontinued immediately.

15. MIXED HEPATITIS (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). - Contest Med 1982; 104:5733-5734. A case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment: - J Covering joint Gastroenterol 1994; 18:168-169. Two cases after 9 and 10 days of treatment at young subjects: - Hepatogastroenterology 1996;43:1015-1019.

16. CHOLESTATIC HEPATITIS (VERY RARE) Five cases: - Press Med 1980; 9:3689-3692.

17. CYTOLYTIC HEPATITIS (RARE) a case, after dosage of only one tablet: - Gastroenterol Covering joint Biol 1992; 16:268.

18. ACUTE PANCREATITIS (VERY RARE) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment: - J Covering joint Gastroenterol 1994; 18:168-169.

19. PSYCHOMOTOR EXCITATION (VERY RARE)

20. NERVOUSNESS (VERY RARE)

21. IRRITABILITY (VERY RARE)

22. INSOMNIA (VERY RARE)

23. SUICIDAL IDEATION (VERY RARE) Seen in: BEGINNING OF TREATMENT

By lifting of psychomotor inhibition. Increase monitoring at the beginning of treatment.

24. ANAPHYLACTIC SHOCK (TO BE CONFIRMED) First case described: - Rev Med Interns 1989; 10:461-462.

25. WITHDRAWAL SYNDROME (FREQUENT)

 Effects on the unborn child 

1. NON-TERATOGENIC IN ANIMALS 2. LACKING INFORMATION IN HUMANS

 Dependence 

1. MAJOR RISK - Pescrire 1990; 10:199. - Therapy 1990; 45:51.

 Precautions for use 

1. GENERAL ANAESTHESIA Discontinue the drug 24 to 48 hours before anaesthesia.

2. PREGNANCY(FIRST TRIMESTER/FIRST THREE MONTHS)

3. BREAST FEEDING

4. OFFICIAL SPORTS/OLYMPICS Prohibited substance: - 7 the Mars Official Journal 2000.

 Contraindications 

1. CHOREA

2. MAO INHIBITORS

3. CHILDREN LESS THAN 1 YEAR OF AGE

4. HYPERSENSITIVITY Known hypersensitivity with amineptine, in particular antecedents of hepatitis after dosage of the product.

 Routes of administration 

- 1 - ORAL

 Dosage and mode of administration 

Adult dosage (oral): 100mg to 200mg per day in one or more doses. Avoid taking in the evening because of the risk of insomnia.

 Pharmacokinetics 

- 1 – RENAL ELIMINATION

Absorption: Peak plasma concentrations 1 to 2 hours after administration of 150mg.

Half-life: 5 to 8 hours.

Elimination: Kidney.

Rapid elimination: two thirds of the administered dose is eliminated in 8 hours.

Bibliography - Europ J Drug Metabolism and Pharmacokinet 1981; 6:123-126. - CNS Drugs 2000; 13:35-45.

Specialities Active ingredient present while constituting single in the following French specialities: • SURVECTOR 100 mg compressed (marketing discontinued) > Active ingredient present while constituting single in the following foreign specialities: • MANEON (ITALY) • SURVECTOR (SPAIN) • SURVECTOR (ITALY) • SURVECTOR (THE PHILIPPINES)

Special thanks and credit to http://www.amineptine.com for detailed information presented here.