Abstract
The advantage of platelet integrin GPIIb-IIIa receptor antagonists in the prevention of thrombotic occlusion was clearly proven in patients who underwent interventional treatment of the coronary artery, but its value in cerebral ischemia is still under investigation. The expectation of intracranial hemorrhage on strong inhibition of platelet function restricts its application in cerebral ischemia. To minimize bleeding while keeping antithrombotic activity, we have tried to find an appropriate approach using a combination of platelet integrin GPIIb-IIIa receptor antagonist and some other antithrombotic agents. The time to thrombotic occlusion was measured using a photothrombotic occlusion model of guinea pig middle cerebral artery. A platelet integrin GPIIb-IIIa receptor antagonist, ME3277 (sodium hydrogen [4-[(4,5,6,7-tetrahydrothieno [3,2-c] pyridin-2-yl) carbonylamino] acetyl-o-phenylene] dioxydiacetate), delayed occlusion time from 7.3 min in vehicle to 15.0, 20.6 and 25.9 min (P<0.05) at 0.1, 0.3 and 1 mg/kg, respectively. ME3277 profoundly inhibited ex vivo platelet aggregation and the highest dose of ME3277 prolonged (3.5 folds, P<0.01) the bleeding time measured in the hind paw. A thromboxane A(2) synthase inhibitor, sod...Continue Reading
References
Jul 1, 1977·Stroke; a Journal of Cerebral Circulation·E F EllisJ A Oates
Aug 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·M HambergB Samuelsson
Jul 1, 1991·Journal of Pharmacological Methods·H MatsunoM Nakashima
May 3, 1991·Cell·D R PhillipsR M Scarborough
May 1, 1990·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·T K Uski, P Reinstrup
Nov 1, 1987·Journal of Cardiovascular Pharmacology·H ShirahaseK Fukui
May 1, 1985·Annals of Neurology·B D WatsonM D Ginsberg
Dec 1, 1985·Thrombosis Research·K NakamuraK Mori
Sep 1, 1984·The Journal of Clinical Investigation·M D McGoon, P M Vanhoutte
Jan 1, 1995·Clinical and Experimental Hypertension : CHE·J L ReidI M Macrae
Dec 15, 1994·Thrombosis Research·J D MacDonaldG M Rodgers
Apr 1, 1993·Neuroreport·M AdnerL Edvinsson
Nov 15, 1997·Thrombosis Research·R C CarrollW C Kouns
Dec 31, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·A ByrneD J Fitzgerald
Jul 28, 1999·European Journal of Pharmacology·K KawanoK Umemura
Mar 4, 2000·Stroke; a Journal of Cerebral Circulation·UNKNOWN Abciximab in Ischemic Stroke Investigators
Jun 9, 1962·Nature·G V BORN