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Titolo:
EFFECT OF 5-HT2 RECEPTOR ANTAGONIST ERGOLINES AND THEIR DESISOPROPYL METABOLITES ON RABBIT PLATELET-AGGREGATION IN-VITRO AND EX-VIVO
Autore:
COHEN ML; BLOOMQUIST W;
Indirizzi:
ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS INDIANAPOLIS IN 46285
Titolo Testata:
Drug development research
fascicolo: 3, volume: 32, anno: 1994,
pagine: 153 - 160
SICI:
0272-4391(1994)32:3<153:EO5RAE>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CANINE CORONARY-ARTERIES; CYCLIC FLOW VARIATIONS; SEROTONIN ANTAGONISTS; DELAYS OCCLUSION; KETANSERIN; BLOCKADE; LY215840; POTENT; MODEL;
Keywords:
RABBIT PLATELET; 5-HT-INDUCED PLATELET AGGREGATION; ERGOLINES; 5-HT2 RECEPTOR ANTAGONISTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
21
Recensione:
Indirizzi per estratti:
Citazione:
M.L. Cohen e W. Bloomquist, "EFFECT OF 5-HT2 RECEPTOR ANTAGONIST ERGOLINES AND THEIR DESISOPROPYL METABOLITES ON RABBIT PLATELET-AGGREGATION IN-VITRO AND EX-VIVO", Drug development research, 32(3), 1994, pp. 153-160

Abstract

Amesergide and LY215840 are potent and long-lasting 5-HT2 receptor antagonists after oral administration to animals. In animals, these ergolines are metabolized to their desisopropyl ergoline congeners which have lower affinity (40-60 nM) at 5-HT2 receptors in the rat relative to higher 5-HT2 receptor affinity (2-3 nM) at the cloned human 5-HT2 receptor. Because amesergide and LY215840 are effective in rabbit modelsof thrombosis, we asked whether their efficacy in the rabbit was related in part to the activity of both the parent and desisopropyl metabolites at rabbit platelet 5-HT2 receptors. Platelet aggregation responses were first optimized to ADP and the combination of ADP and serotonin with regard to platelet number (300,000 platelets/mu l of plasma) and time (70 to 140 min after platelet harvest). In ex vivo studies, both amesergide and LY215840 (3.0 mg/kg p.o.) showed similar and marked antagonism of rabbit platelet 5-HT2 receptors at 1 and 24 h after theiroral administration to rabbits. Furthermore, the desisopropyl ergoline metabolites of both amesergide and LY215840 inhibited serotonin-amplified platelet aggregation responses in vitro as did amesergide and LY215840. Thus, these studies add support to the hypothesis that the desisopropyl metabolites of amesergide and LY215840 may contribute to theoral antithrombotic efficacy of the parent molecules in rabbits. (C) 1994 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 14:10:49