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

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1991年 / 181卷 / 02期

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.

引用

页码：573 / 578

页数：6

共 24 条

[11] MPTP TOXICITY - IMPLICATIONS FOR RESEARCH IN PARKINSONS-DISEASE
KOPIN, IJ
MARKEY, SP
[J]. ANNUAL REVIEW OF NEUROSCIENCE, 1988, 11 : 81 - 96
[12] H-3-SPIPERONE BINDING-SITES IN POST-MORTEM BRAINS FROM SCHIZOPHRENIC-PATIENTS - RELATIONSHIP TO NEUROLEPTIC DRUG-TREATMENT, ABNORMAL MOVEMENTS, AND POSITIVE SYMPTOMS
KORNHUBER, J
RIEDERER, P
REYNOLDS, GP
BECKMANN, H
JELLINGER, K
GABRIEL, E
[J]. JOURNAL OF NEURAL TRANSMISSION, 1989, 75 (01) : 1 - 10
[13] THE PHARMACOLOGY OF THE PARKINSONIAN SYNDROME PRODUCING NEUROTOXIN MPTP (1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE) AND STRUCTURALLY RELATED-COMPOUNDS
MARKEY, SP
SCHMUFF, NR
[J]. MEDICINAL RESEARCH REVIEWS, 1986, 6 (04) : 389 - 429
[14] REGIONAL, REVERSIBLE ULTRASTRUCTURAL-CHANGES IN RAT-BRAIN WITH CHRONIC NEUROLEPTIC TREATMENT
MESHUL, CK
CASEY, DE
[J]. BRAIN RESEARCH, 1989, 489 (02) : 338 - 346
[15] PRESENCE OF 2-METHYL-6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINE AND 1,2-DIMETHYL-6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINE, NOVEL ENDOGENOUS AMINES, IN PARKINSONIAN AND NORMAL HUMAN BRAINS
NIWA, T
TAKEDA, N
YOSHIZUMI, H
TATEMATSU, A
YOSHIDA, M
DOSTERT, P
NAOI, M
NAGATSU, T
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 177 (02) : 603 - 609
[16] IS THE SIGMA-OPIATE RECEPTOR A PROADIFEN-SENSITIVE SUBFORM OF CYTOCHROME-P-450
ROSS, SB
[J]. PHARMACOLOGY & TOXICOLOGY, 1990, 67 (01): : 93 - 94
[17] SCHOOLER NR, 1982, ARCH GEN PSYCHIAT, V39, P486
[18] SIMPSON GM, 1970, ACTA PSYCHIAT SCAND, P11
[19] RESEARCH DIAGNOSTIC CRITERIA - RATIONALE AND RELIABILITY
SPITZER, RL
ENDICOTT, J
ROBINS, E
[J]. ARCHIVES OF GENERAL PSYCHIATRY, 1978, 35 (06) : 773 - 782
[20] IDENTIFICATION OF A POTENTIALLY NEUROTOXIC PYRIDINIUM METABOLITE OF HALOPERIDOL IN RATS
SUBRAMANYAM, B
ROLLEMA, H
WOOLF, T
CASTAGNOLI, N
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 166 (01) : 238 - 244

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