Comparative studies of a new 5HT-uptake inhibitor and some tricyclic thymoleptics

Abstract

The new 5HT-uptake inhibitor, FG 4963, and some tricyclic thymoleptics antagonized p-chloroamphetamine (PCA)-induced hypermotility in rats. FG 4963 was active in about the same s.c. and p.o. doses as chlorimipramine. FG 4963, imipramine and chlorimipramine potentiated hypermotility induced in mice by the 5HT precursor 5HTP, FG 4963 being slightly more active than chlorimipramine. In contrast to the tricyclic thymoleptics FG 4963 did not potentiate the heart rate increasing effect of NA in pithed rats. The peripheral anticholinergic effect of FG 4963 and of desipramine was almost identical while the other imipramine derivatives were more active. All tricyclic thymoleptics were strong peripheral antihistaminics, but FG 4963 was almost devoid of this action. Acute tests for ECG changes in guinea pigs and toxicity in mice and rats showed that FG 4963 and chlorimipramine were less toxic than imipramine and amitriptyline. FG 4963 is presumably a selective 5HT-uptake inhibitor producing much less potentiation of peripheral sympathetic mechanisms than do the tricyclic antidepressants.