YM337, A platelet glycoprotein IIb/IIIa antagonist, lessens photochemically-induced ischemic brain damage in monkeys
✍ Scribed by Seiji Kaku; Kazuo Umemura; Shinya Yano; Ken-ichi Suzuki; Tomihisa Kawasaki; Mitsuyoshi Nakashima
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 206 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
✦ Synopsis
To elucidate the role of platelets in brain damage during focal cerebral ischemia, the effect of YM337, a glycoprotein IIb/IIIa antagonist, on infarct areas and neurologic deficits was measured in monkeys with thrombotic distal middle cerebral artery occlusions. Distal middle cerebral arteries were occluded by a platelet-rich thrombus formed after photochemical reaction between rose bengal dye and green light. The experimental drugs were intravenously injected 30 min after rose bengal injection and continuously infused for 24 h thereafter. YM337, but not the thromboxane A 2 synthetase inhibitor sodium ozagrel, significantly inhibited ex vivo ADP-induced platelet aggregation. The percentage of ADP-induced platelet aggregation 4 h after the start of administration was 87.0% of predosing value in the saline group, 55.6% 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 significantly inhibited thromboxane B 2 generation accompanying arachidonic acid-induced platelet aggregation, YM337 had little effect on this pathway. The neurologic deficit was milder and infarct area significantly smaller in the YM337-treated groups compared with the saline control group. The ratio of infarcted 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 glycoprotein IIb/IIIa is a beneficial approach to treat cerebral artery thrombosis and cerebral infarction. Drug Dev. Res. 45:162-169, 1999.