Identification of potentially neurotoxic pyridinium metabolite in the urine of schizophrenic patients treated with haloperidol.
Evidence that the parkinsonian inducing agent MPTP is biotransformed to a pyridinium species that selectively destroys nigrostriatal neurons in humans and subhuman primates has prompted studies to evaluate the metabolic fate of the structurally related neuroleptic agent haloperidol. With the aid of a highly sophisticated atmospheric pressure ionspray HPLC/MS/MS assay, unambiguous evidence has been obtained for the presence of the haloperidol pyridinium species in extracts of urine obtained from haloperidol-treated patients and in extracts of NADPH-supplemented human liver microsomal incubation mixtures containing haloperidol. The potential significance of the formation of this putative neurotoxic pyridinium species is considered.
Subramanyam
B
B
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg 24061-0212.
Pond
S M
SM
Eyles
D W
DW
Whiteford
H A
HA
Fouda
H G
HG
Castagnoli
N
N
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use / Q000652:urine*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000737:chemistry; D011726:Pyridinium Compounds / Q000032:analysis / Q000737:chemistry / Q000652:urine*; D012559:Schizophrenia / Q000188:drug therapy / Q000652:urine*
D011726:Pyridinium Compounds; D006220:Haloperidol