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Titolo:
NONPEPTIDE GLYCOPROTEIN IIB IIIA INHIBITORS .5. ANTITHROMBOTIC EFFECTS OF MK-0383/
Autore:
LYNCH JJ; COOK JJ; SITKO GR; HOLAHAN MA; RAMJIT DR; MELLOTT MJ; STRANIERI MT; STABILITO II; ZHANG GX; LYNCH RJ; MANNO PD; CHANG CTC; EGBERTSON MS; HALCZENKO W; DUGGAN ME; LASWELL WL; VASSALLO LM; SHAFER JA; ANDERSON PS; FRIEDMAN PA; HARTMAN GD; GOULD RJ;
Indirizzi:
MERCK SHARP & DOHME LTD,RES LABS,DEPT PHARMACOL,WP26-265 W POINT PA 19486 MERCK SHARP & DOHME LTD,RES LABS,DEPT BIOL CHEM W POINT PA 19486 MERCK SHARP & DOHME LTD,RES LABS,DEPT MED CHEM W POINT PA 19486
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 272, anno: 1995,
pagine: 20 - 32
SICI:
0022-3565(1995)272:1<20:NGIII.>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBRINOGEN RECEPTOR ANTAGONIST; ACUTE MYOCARDIAL-INFARCTION; ACTIVATOR-INDUCED THROMBOLYSIS; EVERSION GRAFT RECANALIZATION; CORONARY-ARTERY REPERFUSION; UNSTABLE ANGINA-PECTORIS; ARG-GLY-ASP; PLASMINOGEN-ACTIVATOR; CANINE MODEL; PLATELET-AGGREGATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
61
Recensione:
Indirizzi per estratti:
Citazione:
J.J. Lynch et al., "NONPEPTIDE GLYCOPROTEIN IIB IIIA INHIBITORS .5. ANTITHROMBOTIC EFFECTS OF MK-0383/", The Journal of pharmacology and experimental therapeutics, 272(1), 1995, pp. 20-32

Abstract

The antiaggregatory and antithrombotic actions of MK-0383, a low molecular weight, nonpeptide antagonist of the platelet glycoprotein IIb/IIIa, were evaluated in a variety of canine models. Inhibition of ex vivo platelet aggregation responses to ADP and collagen were observed after the acute sequential i.v. administrations of 10 to 500 mu g/kg or 360-min continuous i.v. infusions of 1 to 10 mu g/kg/min of MK-0383. Hemostatic function normalized within 30 (platelet response to collagen, template bleeding times) to 90 min (platelet response and sensitivity to ADP) after the termination of 360-min i.v. MK-0383 infusions, suggesting no protracted, direct effects on platelet function. With acutesequential i.v. administrations of MK-0383, platelet response to ADP was abolished without significant extension of bleeding time. In a model of platelet-dependent cyclic flow reductions in injured, stenosed left circumflex coronary artery, the bolus i.v. administrations of 300 and 1000 mu g/kg of MK-0383 totally abolished cyclic flow reductions for periods of 18 +/- 1 and 37 +/- 5 min, respectively. In a model of electrically induced left circumflex coronary artery occlusive thrombosis, 10 mu g/kg/min i.v. of MK-0383 initiated 15 min before electrical injury prevented occlusive thrombosis in three of six preparations despite continued electrical stimulation of the vessel for 300 min, delayed occlusion in three of six preparations (160.3 +/- 5.5 min) and reduced thrombus mass(5.1 +/- 1.3 mg), compared to the development of occlusive thrombosis in six of six saline-treated preparations (50.5 +/- 8.7 min; 19.1 +/- 3.0 mg). When administered as an adjunct to thrombolytic agents in the presence of background heparin for lysis of electrically induced left circumflex coronary artery occlusive thrombus, 10 mug/kg/min i.v. of MK-0383 initiated 15 min before tissue-type plasminogen activator or streptokinase increased the incidence of (tissue-typeplasminogen activator: eight of nine MK-0383 vs. three of eight saline; streptokinase: eight of eight MK-0383 vs. two of eight saline) and accelerated reperfusion, and reduced the incidence of acute thromboticreocclusion during continued MK-0383 infusion. These findings indicate significant antithrombotic potential for MK-0383 alone or as an adjunct to thrombolytic therapy in the treatment of coronary artery ischemic syndromes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 21:10:24