CEREBROPROTECTIVE EFFECTS OF A NEVER PYRAZOLINE DERIVATIVE, MS-153, ON FOCAL ISCHEMIA IN RATS

MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) is a novel pyrazol ine compound that has potent cerebroprotective effects in the rat foca l cerebral ischemia model. Middle cerebral artery (MCA) occlusion in r ats allows detailed assessment of both functional and morphological se quelae of brain infarct. Using this model, we evaluated the cerebropro tective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bol us 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 o cclusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 1 2.5 mg/kg/hr infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (2 5.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr) ad ministration was started 6 hr after occlusion.