Pharmacology of amineptine: synthesis and updating

Amineptine is a tricyclic antidepressant agent with the unique capacity to decrease selectively the uptake of dopamine (DA) without affecting the uptake of noradrenaline (NA) and serotonin (5HT). The effect is obtained both in vitro and in vivo by the use of suitable methodology. Amineptine can be differentiated from amphetamine both on the basis of pharmacological as well as biochemical parameters. In vivo, amineptine increases striatal homovanillic acid without affecting the levels of other metabolites of DA, namely, 3, 4, dihydrozoxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3MT). However, by using relatively high doses of amineptine, the extracellular DOPAC level--assessed by the use of pulse voltammetry--was decreased preferentially in the nucleus accumbens but not in the striatum. Chronic treatment with amineptine, as with other antidepressant agents, induces a down-regulation of beta-adrenergic receptors. Amineptine enters the brain and its pharmacological effects are likely due to the unchanged drug rather than to its two main metabolites.