Cerebroprotective effects of a novel pyrazoline derivative, MS-153, on focal ischemia in rats.
MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) is a novel pyrazoline compound that has potent cerebroprotective effects in the rat focal cerebral ischemia model. Middle cerebral artery (MCA) occlusion in rats allows detailed assessment of both functional and morphological sequelae of brain infarct. Using this model, we evaluated the cerebroprotective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 7 days) significantly reduced infarct volumes and improved neurological deficits in MCA occluded rats 7 days after occlusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr) administration was started 6 hr after occlusion.
Kawazura
H
H
Institute of Biological Science, Mitsui Pharmaceuticals, Inc., Chiba, Japan.
Takahashi
Y
Y
Shiga
Y
Y
Shimada
F
F
Ohto
N
N
Tamura
A
A
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy*; D002536:Cerebral Arteries / Q000187:drug effects / Q000601:surgery; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006429:Hemiplegia / Q000188:drug therapy; D006614:Hindlimb / Q000187:drug effects; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
C101692:5-methyl-1-nicotinoyl-2-pyrazoline; D009539:Nicotinic Acids