Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476.
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| Abstract |
A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.
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| Authors | J Kucharczyk, J Mintorovitch, M E Moseley, H S Asgari, R J Sevick, N Derugin, D Norman |
| Journal | Radiology (Radiology) Vol. 179 Issue 1 Pg. 221-7 (Apr 1991) ISSN: 0033-8419 [Print] United States |
| PMID | 2006281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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