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.

Article

作者: Sigg, K ; Radeke, E ; Truog, A ; Ortmann, R ; Delini-Stula, A ; Rogg, H ; Everitt, B J ; Glatt, A ; Jaekel, J ; Buech, O

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.

1984-12-01·European journal of pharmacology3区 · 医学

CGP 4718 A, a new potential antidepressant with a dual mode of action

3区 · 医学

Article

作者: Raymond Bernasconi ; Laurent Maitre ; Aina E. Felner ; Peter A. Baumann ; Peter C. Waldmeier ; Keith F. Tipton

CGP 4718 A (4-[5-chloro-benzofuranyl-2-]-1-methylpiperidine HCl) was found to inhibit MAO A preferentially in vitro in a competitive manner. Assessment of its in vivo effects by an ex vivo approach showed it to be a relatively weak, reversible inhibitor of MAO A. There were also effects on MAO B but they were inferior by a factor of about 10. The onset of the inhibitory effects in rat liver and brain was rapid, being maximal in about 1 h following administration of CGP 4718 A p.o. The inhibition was of relatively short duration with the effects being undetectable 24 h after treatment. CGP 4718 A also inhibited the reuptake of serotonin (5-HT) in synaptosomes in vitro and ex vivo. Evidence for 5-HT uptake inhibition was also found by using the H 75/12 depletor model. Its in vitro and in vivo potency as a 5-HT uptake inhibitor was approximately the same as that of imipramine. The effects on MAO A and on 5-HT uptake occurred over a similar dose range (above 10 mg/kg p.o.) and also had a similar time course. No evidence for inhibitory effects on noradrenaline uptake was found in vivo.

Arzneimittel-Forschung

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

作者: Rogg, H. ; Buech, O. ; Delini-Stula, A. ; Everitt, B. J. ; Jaekel, J. ; Glatt, A. ; Ortmann, R. ; Truog, A. ; Sigg, K. ; Radeke, E.

In psychopharmacol. tests in rats and mice, CGP 4718A (4-(5-chlorobenzofuranyl-2)-1-methylpiperidine HCl)(I) [54403-20-2] exerted 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 4718A 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.Electroencephalog. studies in cats revealed a significant decrease in paradoxical sleep after treatment with CGP 4718A.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 orally.A weak cardiodepressant effect was seen in isolated guinea pig atria.In conclusion, in animal experiments CGP 4718A combines an interesting spectrum of antidepressant, activating and antiaggressive properties with a lack of cardiovascular and tyramine-potentiating effects.

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