Minaprine, a new drug with antidepressant properties.

Minaprine is a new psychotropic drug which has recently proved to be effective in the treatment of various depressive states. In rodents, minaprine exhibits an atypical spectrum of antidepressant and dopaminomimetic activities. Thus in mice minaprine antagonizes the effects of reserpine, decreases immobility time in the behavioural despair test and potentiates the effects of 5-HTP; in rats it antagonizes muricidal behaviour (blocked by PCPA or raphectomy). However, minaprine does not affect yohimbine lethality and does not induce anticholinergic effects in mice. Minaprine also activates central dopaminergic transmission. Thus at low doses the drug antagonizes neuroleptic-induced catalepsy and induces stereotypies in rats. These stereotypies are blocked by neuroleptics. In addition, minaprine (like apomorphine) induces contralateral turning in mice with a unilateral lesion of the striatum, whereas d-amphetamine induces ipsilateral rotations. Unlike classical dopaminomimetic drugs, minaprine does not stimulate locomotor activity in rats. The mechanisms by which minaprine exerts its effects are still unclear, since in vitro minaprine does not affect monoamine uptake or release and does not interact with monoamine receptors. In vivo, minaprine (acute doses) increases 5-HT, decreases 5-HIAA levels in various brain areas and weakly and reversibly inhibits type A MAO; subacute treatments lead to a decrease in the number of 5-HT1 and 5-HT2 receptors. In addition, in the striatum the drug decreases HVA and DOPAC, and increases 3-MT levels, without affecting DA levels. Minaprine also weakly displaces (3H)-spiperone from striatal D2 receptors and increases striatal ACh levels. Finally, minaprine fails to affect brain NA or MHPG levels in acute doses and does not modify beta receptor density in subacute treatment. Thus minaprine appears to be a chemically and pharmacologically original antidepressant drug which activates both 5-HT- and DA-mediated transmission but which is devoid of NAergic and anticholinergic effects. This latter statement is confirmed by the good cardiovascular tolerance of minaprine in dog, monkey and humans, and by the lack of "tricyclic-like" anticholinergic side-effects in man.