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YM337, A platelet glycoprotein IIb/IIIa antagonist, lessens photochemically‐induced ischemic brain damage in monkeys
Author(s) -
Kaku Seiji,
Umemura Kazuo,
Yano Shinya,
Suzuki Kenichi,
Kawasaki Tomihisa,
Nakashima Mitsuyoshi
Publication year - 1999
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199908)47:4<162::aid-ddr2>3.0.co;2-9
Subject(s) - thromboxane a2 , saline , platelet , middle cerebral artery , rose bengal , thromboxane , chemistry , cerebral infarction , anesthesia , antagonist , pharmacology , ischemia , prostaglandin , medicine , thromboxane b2 , receptor , organic chemistry
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. © 1999 Wiley‐Liss, Inc.