Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Hypochlorous acid, a major oxidant produced by activated neutrophils, has low effect on two pyridobenzazepine derivatives, JL 3 and JL 13
Autore:
Liegeois, JF; Zahid, N; Bruhwyler, J; Uetrecht, J;
Indirizzi:
Univ Liege, Med Chem Lab, B-4000 Liege 1, Belgium Univ Liege Liege Belgium 1 Liege, Med Chem Lab, B-4000 Liege 1, Belgium Univ Liege, Physiol Lab, B-4020 Liege, Belgium Univ Liege Liege Belgium B-4020 iege, Physiol Lab, B-4020 Liege, Belgium Univ Toronto, Fac Pharm, Toronto, ON M5S 2S2, Canada Univ Toronto TorontoON Canada M5S 2S2 Pharm, Toronto, ON M5S 2S2, Canada Therabel Res, B-1180 Brussels, Belgium Therabel Res Brussels Belgium B-1180 rabel Res, B-1180 Brussels, Belgium
Titolo Testata:
ARCHIV DER PHARMAZIE
fascicolo: 2-3, volume: 333, anno: 2000,
pagine: 63 - 67
SICI:
0365-6233(200003)333:2-3<63:HAAMOP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED AGRANULOCYTOSIS; CLOZAPINE-ANALOGS; OLANZAPINE; METABOLITE; PYRIDOBENZOXAZEPINE; MYELOPEROXIDASE; DESTRUCTION; OXIDATION; COMPOUND; SYSTEM;
Keywords:
oxidation; antipsychotic; hypochlorous acid; agranulocytosis; pyridobenzazepine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Liegeois, JF Univ Liege, Med Chem Lab, 1 Ave Hop,B36, B-4000 Liege 1, Belgium Univ Liege 1 Ave Hop,B36 Liege Belgium 1 00 Liege 1, Belgium
Citazione:
J.F. Liegeois et al., "Hypochlorous acid, a major oxidant produced by activated neutrophils, has low effect on two pyridobenzazepine derivatives, JL 3 and JL 13", ARCH PHARM, 333(2-3), 2000, pp. 63-67

Abstract

JL 13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b]-[1,5]benzoxazepine fumarate) and JL 3 (10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine), two pyridobenzazepine derivatives structurally related to clozapine, were selected for further development. Due to their structural similarity to clozapine, they are haunted by the spectre of clozapine-induced agranulocytosis. In a previous study, JL 13 was shown to be less sensitive to oxidation than clozapine. In the present paper. using an in vitro procedure, we report the effect of hypochlorous acid (HOCl), a major in vivo oxidant, on both drugs. It appears that the oxidations of JL 3 and JL 13, unlike clozapine, are very slow and little secondary product is formed. Moreover, in contrast to clozapine, the products that were formed are not reactive and thus do not react with glutathione or N-acetylcysteine, Thus, if, as postulated for clozapine, drug-induced agranulocytosis is due to a reactive metabolite formed by neutrophils or their precursors, JL 3 and JL 13 would not beexpected to cause the same adverse reaction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 02:20:47