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The effect of a nonpeptide CC chemokine receptor antagonist, TAK-779, on ischemic brain injury resulting from 1-hour middle cerebral artery occlusion followed by 48-hour reperfusion was examined in ddY mice. On intracerebroventricular injection of vehicle or TAK-779, infarct volume in the vehicle-treated group was 44.2 ± 13.2% of the contralateral hemispheric volume, and TAK-779 (25 and 250 ng/mouse) dose-dependently reduced the infarct volume to 35.0 ± 12.2% and 31.1 ± 12.9%, respectively. On intravenous injection, infarct volume in the vehicle-treated group was 32.0 ± 16.1%, and TAK-779 (5 μg per 20 g body weight) significantly reduced this to 22.0 ± 10.5%. The results showed for the first time that a nonpeptide chemokine receptor antagonist is protective against ischemic brain injury.

TAK-779, A Nonpeptide CC Chemokine Receptor Antagonist, Protects the Brain against Focal Cerebral Ischemia in Mice