NEUROPROTECTIVE EFFECT OF YM-39558 IN FOCAL CEREBRAL-ISCHEMIA IN CATS

We studied the effect of YM-39558, erotic acid ethylester, in a focal cerebral ischemia model in anesthetized cats. YM-39558 has good permea bility across the blood brain barrier, and in the brain is hydrolyzed to erotic acid, the main active substance. Cats were subjected to perm anent occlusion of the middle cerebral artery (MCA) for 6 h, then kill ed and examined histologically. Treatment with YM-39558 (intravenous i nfusion of 11.8 mg (10 mg as erotic acid)/6 ml per kg per h) starting 15 min after MCA occlusion markedly reduced the volume of ischemic dam age (from 2450 +/- 82 mm(3) of the cerebral hemisphere in the saline-t reated cats to 1644 +/- 123 mm(3) in the YM-39558-treated cats, P < 0. 01). In contrast, YM-39558 (2.26 and 1.18 mg/0,8 ml per kg per h) show ed no significant protective effect on ischemic damage. No significant differences were observed between saline- and YM-39558-treated cats c oncerning physiological variables including brain temperature. This ev idence for the neuroprotective efficacy of YM-39558 in gyrencephalic s pecies suggests its therapeutic potential in the treatment of stroke i n humans. (C) 1998 Elsevier Science Ltd. All rights reserved.