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Titolo:
Atypical antipsychotic-induced neutropenia in dogs
Autore:
Lorenz, M; Evering, WE; Provencher, A; Blue, JT; Lewis, HB; Hazelette, JR; Rajagopalan, P; Meunier, PC; Car, BD;
Indirizzi:
Dupont Co, Stine Haskell Res Ctr, Safety Assessment, Newark, DE 19714 USA Dupont Co Newark DE USA 19714 tr, Safety Assessment, Newark, DE 19714 USA AHDL, Endocrine Diag Sect, Lansing, MI 48909 USA AHDL Lansing MI USA 48909 HDL, Endocrine Diag Sect, Lansing, MI 48909 USA Cornell Univ, New York State Coll Vet Med, Ithaca, NY 14853 USA Cornell Univ Ithaca NY USA 14853 State Coll Vet Med, Ithaca, NY 14853 USA Med Management Int VetSmart, Portland, OR 97230 USA Med Management Int VetSmart Portland OR USA 97230 Portland, OR 97230 USA Dupont Merck Pharmaceut Co, Expt Stn, Wilmington, DE 19880 USA Dupont Merck Pharmaceut Co Wilmington DE USA 19880 lmington, DE 19880 USA
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 3, volume: 155, anno: 1999,
pagine: 227 - 236
SICI:
0041-008X(19990315)155:3<227:AANID>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLOZAPINE-INDUCED AGRANULOCYTOSIS; BONE-MARROW; STEM-CELLS; IN-VITRO; MICE; HEMATOPOIESIS; BIOACTIVATION; INCREASE; INVIVO; AGENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Car, BD Dupont Co, Stine Haskell Res Ctr, Safety Assessment, Newark, DE 19714 USA Dupont Co Newark DE USA 19714 ty Assessment, Newark, DE 19714 USA
Citazione:
M. Lorenz et al., "Atypical antipsychotic-induced neutropenia in dogs", TOX APPL PH, 155(3), 1999, pp. 227-236

Abstract

DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically related to clozapine, which exerts its desired pharmacologic effects through selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes. Clozapine therapy is clinically associated with severe granulocytopenia in a small subset of patients. In the course of a 3-month toxicity study in dogs, severe neutropenia, thrombocytopenia, marked myeloid and erythroidleft-shifted bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs' tests, and hypergammaglobulinemia occurred in individual females dosed with 30 mg/kg/day of DMP 406. Related but less severe changes were also observed in males. Sera or purified immunoglobulins from affected and control dogs were tested in methylcellulose-based, canine hematopoieticcolony-forming unit (CFU) assays with or without DMP 406, Neither size nornumber of erythroid or myeloid CFUs differed between cultures containing control or affected dog serum components. Sera from individual affected dogsbut not controls resulted in moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in a concentration-dependent reduction of erythroid and myeloid CFUs with an approximate IC50 of 3.0 mu g/mL. Taken together, DMP 406-induced granulocytopenia and bone marrow dyscrasia appear likely to result from both immune-mediated and direct drug-induced myelotoxicity. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:32:40