Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IN-VITRO EFFECT OF CLOZAPINE ON HEMATOPOIETIC PROGENITOR CELLS
Autore:
DELILIERS GL; SERVIDA F; LAMORTE G; QUIRICI N; SOLIGO D;
Indirizzi:
UNIV MILAN,IRCCS,IST SCI MED,OSPED MAGGIORE,FDN MATARELLI,VIA F SFORZA 35 I-20122 MILAN ITALY OSPED FATEBENEFRATELLI OFTALMICO MILAN ITALY
Titolo Testata:
Haematologica
fascicolo: 10, volume: 83, anno: 1998,
pagine: 882 - 889
SICI:
0390-6078(1998)83:10<882:IEOCOH>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED AGRANULOCYTOSIS; LIMITING DILUTION; RISK-FACTORS; LEUKEMIA; SYSTEM; LINE; DIFFERENTIATION; HEMATOPOIESIS; SCHIZOPHRENIA; METABOLITES;
Keywords:
CLOZAPINE; AGRANULOCYTOSIS; BONE MARROW CULTURES; CD34(+) CELLS; LTC-IC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
G.L. Deliliers et al., "IN-VITRO EFFECT OF CLOZAPINE ON HEMATOPOIETIC PROGENITOR CELLS", Haematologica, 83(10), 1998, pp. 882-889

Abstract

Background and Objective. Clozapine is a diabenzodiazepine derivativecharacterized by a high therapeutic index in schizophrenic patients resistant to traditional neuroleptic drugs, because of the rarity of any extrapyramidal side effects, and its particular hematologic toxicity. According to the international literature, clozapine-induced neutropenia occurs mainly during the first 4-6 months of treatment, and its incidence decreases considerably over time. This neutropenic effect is not dose-dependent and normally clears up after drug discontinuation, although it may evolve into agranulocytosis. The aim of this study is to evaluate the in vitro toxic effect of clozapine and N-desmethylclozapine on both committed and immature human hematopoietic progenitor cells. Design and Methods. Cytotoxic assays were performed in vitro on normal human bone marrow samples treated with clozapine or with its metabolite N-desmethylclozapine. The clonogenic potential after treatmentwith both compounds was assessed on low density mononuclear cells (LD-MNC), purified CD34(+) cells, cytokine driven liquid cultures and long term culture initiating cell (LTC-IC). Results. Clozapine and N-desmethylclozapine had a dose-dependent inhibitory effect on in vitro growth of CFU-GM and BN-E from normal bone marrow. The two drugs had toxiceffects on purified CD34(+) progenitor cells but no significant effect on LTI-IC. Interpretations and Conclusions. Our data indicate a cytotoxic effect, which is more pronounced with N-desmethylclozapine and at high doses, on the committed progenitor cell compartment but not on primitive hematopoietic cells. Furthermore, our data show that clozapine and N-desmethylclozapine have a direct effect on treated cells and do not induce apoptotic death. (C) 1998, Ferrata Storti Foundation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 15:22:26