Behavioral effects and general pharmacology of 4-(5-chloro-benzofuranyl-2)-1-methylpiperidine HC1, an antidepressant inhibiting both monoamine oxidase A and 5-hydroxytryptamine uptake.

In psychopharmacological tests in rats and mice, 4-(5-chloro-benzofuranyl-2)-1-methylpiperidine HC1 (CGP 4718 A) was found to exert behavioral effects typical of both monoamine oxidase (MAO)-A and 5-hydroxytryptamine (5-HT) uptake inhibitors (reserpine antagonism, L-5-HTP potentiation, antiaggressive activity in isolated mice). The potential antidepressant activity of the drug was indicated in rats by antagonism of reserpine and its effect in the social-conflict test. CGP 4718 A did not impair motor coordination and had no influence on locomotor activity up to high doses in mice and rats. In monkeys, it increased directed individual activities, including sex-related behaviors and diminished locomotor activity and passivity. Electroencephalographic studies in cats revealed a significant decrease in paradoxical sleep after treatment with CGP 4718 A. In isolated organs, no significant antagonism of norepinephrine, 5-HT, acetylcholine or histamine was found. Cardiovascular studies in cats showed only transient effects on blood pressure and no effect on heart rate. In conscious dogs no cardiovascular effects were found. No potentiation of the pressor effect of tyramine in rats was detectable after repeated doses of up to 300 mg/kg p.o. A weak cardiodepressant effect was seen in isolated guinea pig atria. In conclusion, in animal experiments CGP 4718 A combines an interesting spectrum of antidepressant, activating and antiaggressive properties with a lack of cardiovascular and tyramine-potentiating effects.