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  • Title: Protective effect of the novel cerebrovascular-selective calcium antagonist (+/-)-(E)-1-(3-fluoro-6, 11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate on ischemic brain damage after permanent middle cerebral artery occlusion in rats.
    Author: Minato H, Honda Y, Masuda Y, Fujitani B, Hosoki K.
    Journal: Arzneimittelforschung; 1996 Jun; 46(6):567-71. PubMed ID: 8767345.
    Abstract:
    In this study the effect of post-ischemic treatment of AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz [b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate, CAS 143110-70-7) a cerebrovascular-selective calcium antagonist, on brain infarction and edema in a rat model of focal cerebral ischemia with permanent middle cerebral artery occlusion (MCAo) was evaluated. Brain infarct size was determined at 24 h after MCAo by measuring 2,3,5-triphenyltetrazolium chloride-negative stained area of the serial brain sections. Post-ischemic treatment of AJ-3941 (3 mg/kg p.o.), 10 min and 3 h after the insult, significantly reduced brain infarct size by 44-80%, compared to vehicle control. The reducing effect was observed both in the cortical and subcortical regions. Three days after MCAo, contents of water and Na+ in the ipsilateral hemisphere significantly increased comparing with those in control rats. Post-ischemic treatment with AJ-3941 (3 and 10 mg/kg twice daily p.o. for 2 days) markedly inhibited the increase in water content and suppressed the increase in Na+ content. In the contralateral hemisphere, these contents showed no significant differences between vehicle-treated group and either control (non-operated) or AJ-3941-treated group. AJ-3941 had only minimum effect on body temperature and physiological parameters, such as blood pressure, blood gases and glucose, even when the maximum dose used (10 mg/kg) was repeatedly administered. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain infarction and edema after permanent focal cerebral ischemia, and they also suggest that AJ-3941 has a beneficial effect in the treatment of ischemic cerebral damage.
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