Anorexigenic and ancillary actions of MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine; CPP)

Abstract

In rats allowed to eat for 2h/day and injected i.p. 30 min before feeding, MK-212, ED₅₀=1.5 mg/kg, was two times more potent as an anorexigen than fenfluramine. However, the compounds were equiactive in the rat following p.o. administration 1.5 or 3 h before the test, while fenfluramine was more potent if the interval was extended to 6 h. In cats permitted to eat for 3 h/day, the ED₅₀ dose (mg/kg p.o.) for MK-212 determined at 0.5, 1 and 3 h after feeding was, respectively, 15, 10 and 3 times less than that of fenfluramine. Emesis and diarrhea were frequently observed ancillary effects in cats treated with fenfluramine, whereas apparent sedation and salivation were commonly detected in animals after MK-212. In rats or cats pretreated with methergoline, the decrease in food consumption elicited by MK-212 was markedly inhibited, suggesting that the mechanism of action involves a serotoninlike effect. Compared with the marked stimulant action of amphetamine, MK-212 had only a minor and inconsistent effect on motor activity in rats and mice. Similar results were obtained with fenfluramine. MK-212 was not self-administered by rats, while the self-administration of amphetamine and morphine were demonstrated using the same experimental protocol.