TAK-779, a nonpeptide CC chemokine receptor antagonist, protects the brain against focal cerebral ischemia in mice

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 mug per 20 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 in jury.