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NEUROLOGY 1988;38:1667
© 1988 American Academy of Neurology

(S)-Emopamil, a novel calcium channel blocker and serotonin S2 antagonist, markedly reduces infarct size following middle cerebral artery occlusion in the rat

Hitoshi Nakayama, MD, Myron D. Ginsberg, MD and W. Dalton Dietrich, PhD

Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, FL.

(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.

Address correspondence and reprint requests to Dr. Ginsberg, Department of Neurology (D4-5), University of Miami, School of Medicine, P.O. Box 016960, Miami, FL 33101.

Supported in part by a grant from Knoll A. G., Ludwigshafen, Federal Republic of Germany; by USPHS grants NS-05820 and NS-22603; and by Grants-in-Aid of the American Heart Association, with funds contributed in part by the Florida Affiliate and the Greater Miami Chapter. Dr. Ginsberg is the recipient of a Jacob Javits Neuroscience Investigator Award. Dr. Dietrich is an Established Investigator of the American Heart Association.

Received June 16, 1988. Accepted for publication in final form August 17, 1988.




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