Side-chain degradation and ring hydroxylation of pehnothiazine tranquilizers.

Abstract

In confirmation of an earlier report from this laboratory, promazine and chlorpromazine have have been found to undergo side-chain cleavage as a minor route of metabolism. Phenothiazine sulfoxide appears to be the most significant degradation product of promazine which is excreted by man (0.4% of dose) and dogs (0.8%). It is present in urine in both free and bound forms, accompanied by traces of phenothiazine, 3-hydroxyphenothiazine and phenothiazine. In similar manner, chlorpnomazine is degraded to form 2-chlorophenothiazine sulfoxide and traces of 2-chlorophenothiazine, 2-chloro-7-hydroxyphenothiazine, 2-chlorophenothiazone and 2-ehlorothionol. Dogs excrete two series of phenolic derivatives of chlorpromazine. One is hydroxylated at position 7 (major site), the other at position 3. The human phenolic metabolites are principally of the 7-hydroxy series, accompanied by smaller amounts of phenols which are thought to have the 3, 7-dioxy configuration.