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Titolo:
ANTITHROMBOTIC EFFECTS OF DMP-728, A PLATELET GPIIB IIIA RECEPTOR ANTAGONIST, IN A CANINE MODEL OF ARTERIAL THROMBOSIS/
Autore:
ROTE WE; DAVIS JH; MOUSA SA; REILLY TM; LUCCHESI BR;
Indirizzi:
UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,M6322 MED SCI BLDG 1 ANN ARBOR MI 48109 UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,M6322 MED SCI BLDG 1 ANN ARBOR MI 48109 DUPONT MERCK CO WILMINGTON DE 00000
Titolo Testata:
Journal of cardiovascular pharmacology
fascicolo: 4, volume: 23, anno: 1994,
pagine: 681 - 689
SICI:
0160-2446(1994)23:4<681:AEODAP>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
IIB IIIA RECEPTOR; MONOCLONAL-ANTIBODIES; PLASMINOGEN-ACTIVATOR; GLYCOPROTEIN-IIB/IIIA; UNSTABLE ANGINA; THROMBOLYSIS; FIBRINOGEN; ADHESION; RETHROMBOSIS; AGGREGATION;
Keywords:
PLATELETS; CANINE; CAROTID ARTERY; GLYCOPROTEIN-IIB/IIIA; ANTITHROMBOTIC; PEPTIDOMIMETIC; THROMBOLYSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
W.E. Rote et al., "ANTITHROMBOTIC EFFECTS OF DMP-728, A PLATELET GPIIB IIIA RECEPTOR ANTAGONIST, IN A CANINE MODEL OF ARTERIAL THROMBOSIS/", Journal of cardiovascular pharmacology, 23(4), 1994, pp. 681-689

Abstract

The platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa, fibrinogen receptor) represents the final common pathway for platelet aggregation. Inhibition of GPIIb/IIIa with antibodies or peptides containing the RGD sequence has been reported to prevent arterial thrombosis. We examined DMP 728 -arginyl-glycyl-L-aspartyl-3-(amino-methyl-benzoic acid], methanesulfonic acid salt], a cyclic peptidomimetic, GPIIb/IIIa receptor antagonist, for prevention of thrombosis and rethrombosis in a canine model of carotid artery thrombosis. Dogs were anesthetized, and both carotid arteries were instrumented with an electrode, a flow probe, and a stenosis. A 300-muA current was applied to the intimal surface in the right carotid artery (RCA, control) through the electrode; time to occlusive thrombus formation and thrombus mass was noted. The RCA served as the control vessel; the left carotid artery (LCA) served as the test vessel after DMP 728 administration (0.1 or 1.0 mg/kg, intravenously, i.v.). As compared with controls, occlusive thrombus formationwas reduced by both doses of DMP 728 (control 100% n = 12; 0.1 mg/kg i. v. 17%, p < 0.05, n = 6; 1.0 mg/kg i.v. 0%, p < 0.05, n = 6), time to occlusion was increased (p < 0.05), and thrombus weight was reduced(p < 0.05). Ex vivo platelet aggregation was inhibited in all groups. In a second group of animals, a carotid artery thrombus was formed and lysed with anisoylated plasminogen activator complex (APSAC; 0.05 U/kg intraarterially, i.a.) with or without DMP 728. Dogs receiving saline demonstrated a 100% rate of rethrombosis as compared with 25% of DMP 728-treated dogs reoccluding after recannalization (p < 0.05). Competition binding analysis showed that DMP 728 can prevent binding of 7E3GPIIb/IIIa antibody to platelets in vitro. The data suggest that DMP 728 may have therapeutic potential as an effective antithrombotic agent by inhibiting the platelet-fibrinogen interaction representing the final common pathway in platelet-dependent thrombus formation.

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Documento generato il 28/11/20 alle ore 01:01:23