Hiroshi Kawazura (1), Yasuhiro Takahashi (1), Yoshio Shiga (1), Fumiki Shimada (1), Norio Ohto (1,*) and Akira Tamura (2)
(1) Institute of Biological Science, Mitsui Pharmaceuticals, Inc.,
1900-1 Togo, Mobara, Chiba 297, Japan
(2) Department of Neurosurgery, Teikyo University, School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173, Japan
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: MS-153, Middle cerebral artery occlusion, Focal cerebral
ischemia, Cerebroprotection, Therapeutic window