YM337, a platelet glycoprotein IIb/IIIa antagonist, lessens photochemically-induced ischemic brain damage in monkeys

To elucidate the role of platelets in brain damage during focal cerebral is chemia, the effect of YM337, a glycoprotein IIb/IIIa antagonist, on infarct areas and neurologic deficits was measured in monkeys with thrombotic dist al middle cerebral artery occlusions. Distal middle cerebral arteries were occluded by a platelet-rich thrombus formed after photochemical reaction be tween rose bengal dye and green light. The experimental drugs were intraven ously injected 30 min after rose bengal injection and continuously infused for 24 h thereafter. YM337, but not the thromboxane A(2) synthetase inhibit or sodium ozagrel, significantly inhibited ex vivo ADP-induced platelet agg regation. The percentage of ADP-induced platelet aggregation 4 h after the start of administration was 87.0% of predosing value in the saline group, 5 5.6% in the YM337 low dose group, 28.8% in the YM337 high dose group and 89 .0% in the sodium ozagrel group. However, while sodium ozagrel significantl y inhibited thromboxane B-2 generation accompanying arachidonic acid-induce d platelet aggregation, YM337 had little effect on this pathway. The neurol ogic deficit was milder and infarct area significantly smaller in the YM337 -treated groups compared with the saline control group. The ratio of infarc ted area to the whole area of the cerebrum was 12.3% in the saline group, 5 .5% in the YM337 low dose group, 5.7% in the YM337 high dose group, and 11. 0% in the ozagrel group. These results suggest that a blockade of glycoprot ein IIb/IIIa is a beneficial approach to treat cerebral artery thrombosis a nd cerebral infarction. (C) 1999 Wiley-Liss, Inc.