Evolutionary trend in the metabolic oxidation of chlorpromazine.

The metabolism of the widely used antipsychotic drug chlorpromazine has been investigated in man, five mammalian and four non-mammalian species, and 7-hydroxylation was found to be the major metabolic route. All of the previously reported major oxidized metabolites were excreted by man, rhesus monkey and capuchin monkey, while sulfoxidation was extensive in rat and N-demethylation in rabbit. Lizard and tortoise did not form sulfoxides, and tortoise was unable to N-demethylate the drug. Toad, pigeon and cat had limited capability for these two metabolic pathways.