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 microg 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.
Takami
Shinya
S
Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Minami
Masabumi
M
Katayama
Takahiro
T
Nagata
Izumi
I
Namura
Shobu
S
Satoh
Masamichi
M
D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000473:pathology; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D020768:Middle Cerebral Artery / Q000601:surgery; D009195:Peroxidase / Q000032:analysis; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D000577:Amides; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D000644:Quaternary Ammonium Compounds; C119369:TAK 779; D009195:Peroxidase