Prolongation of certain effects of amphetamine by chlorpromazine

Abstract

This study examines the effect of chlorpromazine on the hypermotility and hyperthermia induced by amphetamine in rats and correlates the effects observed with brain levels of the stimulant. Chlorpromazine antagonized these effects of amphetamine initially, and there was a dose–effect relationship in this antagonism. On the other hand, a combination of 7.2 mg/kg chlorpromazine and 8.5 mg/kg dl-amphetamine caused a delayed excitation and hyperthermia. The excitatory effect of this dose of amphetamine was prolonged by doses of chlorpromazine ranging from 1.9 to 7.2 mg/kg. Chlorpromazine modified the disposition of amphetamine as evidenced by considerably higher and more sustained brain levels of the stimulant in rats which received the combined treatment. The significance of these findings and the similarity of the interaction of chlorpromazine and imipramine with amphetamine are discussed.