US EPA

8096180 

Journal Article 

The new antidepressant pirlindole. A comparison with imipramine and tranylcypromine 

Martorana, PA; Nitz, RE 

1979 

1 

Arzneimittel-Forschung
ISSN: 0004-4172
EISSN: 1616-7066 

29 

6 

946-949 

English 

The new antidepressant 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride (pirlindole) was compared to imipramine and tranylcypromine in a series of pharmacological tests. Pirlindole antagonized in a dose-related manner reserpine-induced ptosis and hypothermia in mice. In this regard it was more potent than imipramine but less than tranylcypromine. Its duration of action was double that of imipramine but shorter than that of tranylcypromine. Pirlindole antagonized both tetrabenazine-induced ptosis and catalepsy at similar doses, whereas imipramine and tranylcypromine were significantly more potent against ptosis than against catalepsy (rat). Pirlindole was inactive against fluphenazine induced catalepsy (rat) where both imipramine and tranylcypromine were active. In the immobility test in rats pirlindole was slightly more potent than imipramine but less potent than tranylcypromine. Pirlindole and imipramine had similar LD's50 (mouse), the LD50 of tranylcypromine was approximately 3 times lower than that of pirlindole. Pirlindole, contrary to imipramine but similar to tranylcypromine, did not antagonize oxotremorine-induced tremor in mice, however, it potentiated oxotremorine-induced hypothermia while imipramine and tranylcypromine antagonized it. Pirlindole and tranylcypromine potentiated tryptamine (rat) and 1,5-hydroxytryptophan (mouse)-induced symptomatology. Pirlindole, however, was markedly less potent and shorter-lasting than tranylcypromine. These results show pirlindole is quantitatively and qualitatively different from imipramine and tranylcypromine.