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.
Ablordeppey
S Y
SY
Department of Medicinal Chemistry, University of Mississippi, University 38677.
Borne
R F
RF
Davis
W M
WM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D005615:Freezing; D006220:Haloperidol / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D011894:Rana pipiens
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006220:Haloperidol