(S)‐Emopamil, a novel calcium channel blocker and serotonin S 2 antagonist, markedly reduces infarct size following middle cerebral artery occlusion in the rat

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Abstract
(S)-Emopamil is a novel calcium channel blocker of the phenylalkylamine class, with superior blood-brain permeability and potent serotonin S2 antagonist activity. In this study, we investigated the effects of (S)-emopamil on the histopathologic consequences of permanent middle cerebral artery (MCA) occlusion in anesthetized Sprague-Dawley rats. In three treatment protocols, intraperitoneal (S)-emopamil therapy was begun either 30 minutes prior to, immediately after, or 1 hour after MCA occlusion. Nontreated and saline-treated control groups were also studied. Cortical infarct volumes in nontreated and saline-treated control rats were 85 ± 22 and 66 ± 19 mm3 (mean ± SD), respectively, and did not differ statistically from one another. Corresponding cortical infarct volume values in (S)-emopamil-pretreated rats, and in rats with post-treatment at 0 hours and 1 hour, were 33 ± 23, 29 ± 14, and 27 ± 16 mm3, respectively; each of these was significantly smaller than control values. In contrast to the neocortex, striatal infarct volume was not altered by (S)-emopamil treatment. The results of this study demonstrate the marked therapeutic efficacy of (S)-emopamil in focal cortical infarction, even when treatment is delayed for 1 hour following MCA occlusion.