Abstract

The effects of chlorpromazine, chlorpromazine sulfoxide, monomethylchlorpromazine, chlorpromazine-N-oxide, promazine, 2-hydroxypromazine, and 4-hydroxypromazine on potentiation of hexobarbital sleeping time, on stimulated locomotor activity (rotating rod) and on conditioned responses controlled by reward or punishment have been examined in the rat and mouse.

In all tests, chlorpromazine sulfoxide was the least active of the compounds. Chlorpromazine-N-oxide, although active, was less active than chlorpromazine or monomethylchlorpromazine. A lag in onset of activity, which was not seen for any of the other drugs, was noted with chlorpromazine-N-oxide in both conditioned response tests. Monomethylchlorpromazine was generally only slightly less active than chlorpromazine.

In the promazine series, 4-hydroxypromazine was about equally as active or somewhat less active than promazine. 2-Hydroxypromazine was markedly less active than promazine except in the sleeping time test when administered by the intravenous route. In this case, it was about as active as promazine.

Promazine was less active than chlorpromazine in all tests.

The findings reported are consistent with the thesis that, at least in animals, the effects of chlorpromazine and promazine may be due in part to some of the metabolites of the drugsdemethylated, hydroxylated, and demethylated hydroxylated metabolites in particular.