Nomifensine enantiomers: Psychopharmacological effects in mice and rats in comparison with D,L‐nomifensine

Abstract

AbstractThe D‐ and L‐enantiomers of nomifensine (8‐amino‐2‐methyl‐4‐phenyl‐1,2,3,4‐tetrahydrois‐oquinoline) were tested for psychopharmacological effects in mice and rats with D,L‐nomifensine hydrogen maleate as a reference drug. In tests on antidepressant activity (antagonism of tetrabenazine ptosis, reserpine hypothermia, oxotremorine hypothermia, “behavioral despair,” and potentiation of yohimbine toxicity), the D‐enantiomer was on average 1.7 or 2.8 times more potent than the racemate with the intraperitoneal (i.p.) or oral route of administration, respectively. The L‐enantiomer displayed slight ativity only when injected i.p. and was on average ≥ 30 times less potent than the racemate. In tests on dopaminergic acivity, D‐nomifensine was about 3 times (motor stimulation in mice) or 1.5–1.9 times (induction of stereotyped behavior in rats) more potent than the racemate. The L‐enantiomer was devoid of stimulant or stereotypic activity and had a rather sedative effect. In acute (24 h) toxicity studies, D‐nomifensine proved 2.9 or 4.5 times more toxic, and L‐nomifensine was 1.6 or 1.3 times less toxic than the racemate (i.p. or p.o., respectively). The results indicate that nomifensine acts by stereospecific mechanisms and that the D‐enantiomer is the active component.