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Titolo:
Comparative oxidation of loxapine and clozapine by human neutrophils
Autore:
Jegouzo, A; Gressier, B; Frimat, B; Brunet, C; Dine, T; Luyckx, M; Kouach, M; Cazin, M; Cazin, JC;
Indirizzi:
Fac Sci Pharmaceut & Biol, Lab Pharmacol Pharmcocinet & Pharm Clin, F-59006 Fac Sci Pharmaceut & Biol Lille France F-59006 net & Pharm Clin, F-59006 Fac Med, Serv Commun Spectrometrie Masse Lille 2, F-59045 Lille, France Fac Med Lille France F-59045 metrie Masse Lille 2, F-59045 Lille, France
Titolo Testata:
FUNDAMENTAL & CLINICAL PHARMACOLOGY
fascicolo: 1, volume: 13, anno: 1999,
pagine: 113 - 119
SICI:
0767-3981(1999)13:1<113:COOLAC>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED AGRANULOCYTOSIS; MYELOPEROXIDASE SYSTEM; N-DESMETHYLCLOZAPINE; HYPOCHLOROUS ACID; IN-VITRO; CHLORINATION; METABOLITES; MANAGEMENT; MARKER; CELLS;
Keywords:
loxapine; clozapine; agranulocytosis; myeloperoxidase; human polymorphonuclear neutrophils;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Gressier, B Facrofesseurmaceut & Biol, Lab Pharmacol Pharmcocinet & Pharm Clin, 3 Rue P Fac Sci Pharmaceut & Biol 3 Rue Professeur Laguesse,BP 83 Lille France F-59006
Citazione:
A. Jegouzo et al., "Comparative oxidation of loxapine and clozapine by human neutrophils", FUN CL PHAR, 13(1), 1999, pp. 113-119

Abstract

The clozapine-induced agranulocytosis could be due to the formation of a reactive intermediate formed in polymorphonuclear neutrophils and granulocyte precursors with the myeloperoxidase-hydrogen peroxide system. On the contrary, no case of agranulocytosis has been described for loxapine, an other neuroleptic drug with a Very close structural analogy. We have compared theclozapine and loxapine interaction with the oxidative burst and particularly with this enzymatic complex. On the one hand, the assay of the oxidativespecies demonstrated a different impact for the two neuroleptics. The 50% inhibitory concentration was 92 mu M for hydrogen peroxide and 40 mu M for hypochlorous acid for loxapine. The loxapine target is located before the myeloperoxidase-hydrogen peroxide system in the oxidative stream, whereas clozapine diverts the chlorination pathway of the enzyme. On the other hand, the in vitro metabolism of drugs by the myeloperoxidase-hydrogen peroxide system has been investigated by mass spectrometry. Loxapine remains inert but clozapine undergoes the oxidation. The glutathione or ascorbate addition in the medium leads to a removal of the oxidation. Glutathione is able to trap the toxic intermediate and could avoid its formation. (C) Elsevier, Paris.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 00:52:04