title: (S)-emopamil, a novel calcium channel blocker and serotonin S2 antagonist, markedly reduces infarct size following middle cerebral artery occlusion in the rat.
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.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, FL 33101.
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: M D
authors.initials: MD
authors.lastname: Ginsberg
authors.forename: W D
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000627:therapeutic use; D014700:Verapamil / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D012702:Serotonin Antagonists; D014700:Verapamil; C052752:emopamil