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Titolo:
THE POSSIBLE ROLE OF AN ACTIVE METABOLITE DERIVED FROM THE NEUROLEPTIC AGENT HALOPERIDOL IN DRUG-INDUCED PARKINSONISM
Autore:
IGARASHI K;
Indirizzi:
KOBEGAKUIN UNIV,FAC PHARMACEUT SCI,LAB BIOCHEM TOXICOL,NISHI KU KOBE HYOGO 65121 JAPAN
Titolo Testata:
Journal of toxicology. Toxin reviews
fascicolo: 1, volume: 17, anno: 1998,
pagine: 27 - 38
SICI:
0731-3837(1998)17:1<27:TPROAA>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROTOXIC PYRIDINIUM METABOLITE; METHYLATED BETA-CARBOLINIUM; FREELY MOVING RATS; DOPAMINERGIC NEUROTOXIN; HUMAN-BRAIN; INTRACEREBRAL MICRODIALYSIS; ENVIRONMENTAL TOXINS; N-METHYLATION; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
57
Recensione:
Indirizzi per estratti:
Citazione:
K. Igarashi, "THE POSSIBLE ROLE OF AN ACTIVE METABOLITE DERIVED FROM THE NEUROLEPTIC AGENT HALOPERIDOL IN DRUG-INDUCED PARKINSONISM", Journal of toxicology. Toxin reviews, 17(1), 1998, pp. 27-38

Abstract

This report summarizes the case for development of extrapyramidal side-effects associated with chronic haloperidol (HP) use, such as drug-induced parkinsonism and tardive dyskinesia. The involvement of neurotoxic metabolites has been proposed as an idea,The results from metabolic studies have demonstrated that HP is oxidatively converted to the pyridinium metabolite, (4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl] pyridinium species (HPP+), which structurally resembles the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium species (MPP+). The conversion is mediated by the CYP3A isoform of cytochrome P450 in the Livermicrosomes of animals and humans. HPP+ levels in rat brain increased gradually after intraperitoeal administration of HP. Moreover, in vivomicrodialysis techniques revealed HPP+ in rat brain following administration of HP. lt may have been formed peripherally and then transported through the blood-brain barrier. The results from intracerebral microdialysis and neuronal cell culture studies have shown that the pyridinium metabolite HPP+ derived from HP has toxic effects on dopaminergic and serotonergic neurons resembling those of the neurotoxin MPP+. Therefore, it is possible that the active metabolite of haloperidol, HPP, may be involved in the development of extrapyramida side-effects with chronic HP therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 19:15:15