Amineptine

Originator

Survector,Eutherapie,France,1978

The Uses of Amineptine

Amineptine is used as an atypical tricyclic antidepressant. Amineptine selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine.

Definition

ChEBI: A carbocyclic fatty acid that is 5-aminoheptanoic acid in which one of the hydrogens attached to the nitrogen is replaced by a 10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl group. A tricyclic antidepressant, it w s never approved in the US and was withdrawn from the French market in 1999 due to concerns over abuse, dependence and severe acne.

Manufacturing Process

6.5 g of 5-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene in 60 ml of nitromethane and 10.8 g of ethyl 7-aminoheptanoate in 12ml of nitromethane were mixed at ambient temperature. The reaction was slightly exothermic. The reaction mixture was left to stand overnight and the solvent was evaporated in vacuum. The residue was taken up in normal hydrochloric acid and the resulting precipitate was filtered off.
10.5 g of crude ethyl 7-[dibenzo(a,d)cycloheptadiene-5-yl]aminoheptanoate hydrochloride were obtained, of which a sample recrystallized from benzene gave a pure product melting instantaneously at 166°C to 168°C.
The hydrochloride of the crude ester obtained above was added to 25 ml of 2 N hydrochloric acid. The whole was kept under reflux for 2 hours. The material dissolved and a new hydrochloride then reprecipitated. After cooling, the hydrochloride of the crude acid was filtered off, washed with iced water and then recrystallized from distilled water. 5.7 g of 7- [dibenzo(a,d)cycloheptadienb-yl] aminoheptanoic acid hydrochloride were obtained, melting instantaneously at 226°C to 230°C.

Therapeutic Function

Central stimulant

Enzyme inhibitor

This synthetic dopamine reuptake inhibitor (FW = 338.47 g/mol; CAS 57574-09-1), also known by the trade names Survector?, Maneon?, Directim?, Neolior?, Provector?, and Viaspera? as well as its IUPAC name, 7-[(10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-yl)amino]heptanoic acid, significantly reduces the effect of 6-hydroxy-dopamine on brain dopamine, increases striatal homovanillic acid concentrations, and shows cross-tolerance. Despite these amphetamine-like properties, amineptine does not alter brain noradrenaline or acetylcholine concentrations, suggesting amineptine is a new type of antidepressant with a brain biochemical profile differing from that of other drugs used in depressive disorders. Amineptine is also a norepinephrine reuptake inhibitor. This agent is also ineffective in reducing amphetamine withdrawal symptoms or craving. Amineptine failed to secure FDA approval and is not a duly authorized drug in the U.S.