Abstract

CI-634 acts principally on the central nervous system. Species of animals vary markedly in response to the drug. Excitement and ataxia prevailed in mice and rats at low doses of 01-634. At high doses, surgical anesthesia occurred in monkeys and cats, and either light anesthesia or transitory clonic seizures occurred in dogs. Anesthesia was induced in monkeys and cats within 2 to 3 mm after im. administration. No cumulative effect or tolerance development resulted upon repeated administration of CI-634. Catalepsy was the characteristic effect of CI-634 in all animal species. At cataleptic doses, it augmented the depth and duration of anesthesia produced by other anesthetic agents without causing an increase in respiratory depression. It produced slight hypertension and tachycardia in unanesthetized dogs. Only negative chronotropic and inotropic effects of CI-634 were observed in the isolated rabbit heart. The lack of a direct sympathomimetic effect of CI-634 was evident by its failure to influence the blood pressure responses to norepinephrine and phenethylamine in anesthetized dogs and by its failure to increase the perfusion pressure in the autoperfused hindquarter of the dog after direct i.a. injection. The hypertension and tachycardia produced by CI-634 appeared to be the result of an influence on central cardiovascular regulatory mechanisms.