Freezing action of a metabolite of haloperidol in frogs

In vivo metabolism studies led to the identification of a previously proposed metabolite of haloperidol, 4-(4'-chlorophenyl)-4-piperidinol (CPPO), in the liver of a haloperidol-treated rat. However, the secondary metabolites of CPPO that we have proposed were not observed in this study. Neurotoxicity studies in frogs, which have been used to detect N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) action, showed that CPPO did not mimic the neurotoxicity of MPTP but caused a delayed and persistent freezing action in Rana pipiens frogs. It is proposed that this action may contribute to some of the delayed side-effects associated with haloperidol therapy.