IDENTIFICATION OF POTENTIALLY NEUROTOXIC PYRIDINIUM METABOLITE IN THE URINE OF SCHIZOPHRENIC-PATIENTS TREATED WITH HALOPERIDOL

被引:82
作者
SUBRAMANYAM, B
POND, SM
EYLES, DW
WHITEFORD, HA
FOUDA, HG
CASTAGNOLI, N [1 ]
机构
[1] VIRGINIA POLYTECH INST & STATE UNIV, DEPT CHEM, BLACKSBURG, VA 24061 USA
[2] UNIV QUEENSLAND, PRINCESS ALEXANDRA HOSP, DEPT MED, WOOLLOONGABBA, QLD 4102, AUSTRALIA
[3] WOLSTON PK HOSP, CLIN STUDIES UNIT, WACOL, QLD 4076, AUSTRALIA
关键词
D O I
10.1016/0006-291X(91)91228-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. © 1991.
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页码:573 / 578
页数:6
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