(S)-emopamil protects against global ischemic brain injury in rats

Abstract

(S)-Emopamil is a novel calcium channel blocker of the phenylalkylamine class, with potent serotonin S2 antagonist activity. We investigated the effect of (S)-emopamil on the histopathologic consequences of global brain ischemia in anesthetized rats. Pretreated rats (n = 15) received 20 mg/kg i.p. (S)-emopamil 30 minutes before and 2 hours following 10 minutes of bilateral common carotid artery occlusion plus arterial hypotension (50 mm Hg). Quantitative cell counts following 3 days' survival revealed a marked loss of pyramidal neurons in all subsectors of the hippocampal CA1 area of untreated ischemic rats (n = 15). In contrast, in (S)-emopamil pretreated rats numbers of normal neurons were significantly higher, by 2.4-, 1.9-, and 1.8-fold, respectively, in the medial, middle, and lateral subsectors of the CA1 area. For example, normal neuron counts in the medial CA1 subsector were 34 +/- 9 (mean +/- SEM) in untreated ischemic rats compared with 82 +/- 13 in (S)-emopamil pretreated rats (control nonischemic value [n = 5] 157 +/- 2). By semiquantitative grading, (S)-emopamil also decreased ischemic changes in the cerebral cortex. No significant effect of (S)-emopamil on ischemic injury was detected in rats treated beginning 30 minutes after the ischemic insult (n = 10). Thus, pretreatment with (S)-emopamil is beneficial in decreasing the severity of neuronal injury in global brain ischemia.