Differential Antagonism of Reserpine Eyelid Closure by Imipramine and Amphetamine

Abstract

Oral treatment of mice with imipramine, an antidepressant (50 to 200 mg base/kg/day) or with amphetamine, a stimulant, (4 to 64 mg base/kg/day) for at least two consecutive days, followed by intraperitoneal challange with reserpine (2.5 mg/kg) 24 hours after the last drug treatment, produced a differential antagonism to reserpine-produced eyelid closure; only imipramine produced appreciable antagonism. On the other hand, with single administration of the drugs followed by reserpine challenge one hour later, both amphetamine and imipramine were equally active, but higher doses of imipramine were required. These results indicate that the antagonism to reserpine-produced eyelid closure resulting from imipramine lasts longer than that from amphetamine. This difference is similar to differences seen with these compounds in man; amphetamine is a shorter acting drug than imipramine. Possibly the difference of effects observed by us is indicative of a different mechanism of action.