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Titolo:
Distribution of clozapine and desmethylclozapine between blood and brain in rats
Autore:
Weigmann, H; Hartter, S; Fischer, V; Dahmen, N; Hiemke, C;
Indirizzi:
Univ Mainz, Dept Psychiat, D-55131 Mainz, Germany Univ Mainz Mainz Germany D-55131 , Dept Psychiat, D-55131 Mainz, Germany
Titolo Testata:
EUROPEAN NEUROPSYCHOPHARMACOLOGY
fascicolo: 3, volume: 9, anno: 1999,
pagine: 253 - 256
SICI:
0924-977X(199903)9:3<253:DOCADB>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
REFRACTORY SCHIZOPHRENIC-PATIENTS; MAJOR METABOLITES; PLASMA CLOZAPINE; ANTIPSYCHOTIC AGENT; CLINICAL-RESPONSE; SERUM;
Keywords:
clozapine; desmethylclozapine; serum; brain; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Hiemke, C Univ Mainz, Dept Psychiat, Untere Zahlbacher Str 8, D-55131 Mainz, Germany Univ Mainz Untere Zahlbacher Str 8 Mainz Germany D-55131 ermany
Citazione:
H. Weigmann et al., "Distribution of clozapine and desmethylclozapine between blood and brain in rats", EUR NEUROPS, 9(3), 1999, pp. 253-256

Abstract

Desmethylclozapine is the major metabolite of clozapine in serum. Althoughthe metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrationsof clozapine that are considered as therapeutically effective in man. Desmethyl clozapine concentrations exceeded those of clozapine at 2-5 h after drug application. In brain, drug concentrations were 15.8-fold higher for clozapine than in serum, but only 2.7-fold higher for desmethylclozapine. Thebrain clozapine concentrations exceeded those of desmethylclozapine by about 3 times. These data indicate that desmethylclozapine is unlikely to playa role for CNS-mediated effects. (C) 1999 Elsevier Science B.V. All rightsreserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 15:17:13