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The effects of a novel opioid kappa-receptor agonist U-50488H on Na(+)-K(+)-adenosine triphosphatase (ATPase) activity and regional cerebral blood flow (rCBF) were studied in the acute ischemic brain of rats after middle cerebral artery (MCA) occlusion. Administration of U-50488H 15 minutes prior to MCA occlusion attenuated ischemic reduction in Na(+)-K(+)-ATPase activity 15 minutes after MCA occlusion. The effect was statistically significant at a dosage of 30 mg/kg, but not at lower doses (0.3 and 3 mg/kg). There was no effect on rCBF before MCA occlusion, and the decreased flow after occlusion was enhanced with a significant fall in systemic blood pressure at a dosage of 30 mg/kg. These results indicate that U-50488H has therapeutic potential in cerebral ischemia by mechanisms other than improvement in CBF.

Potential Protection by a Specific Kappa-opiate Agonist U-50488H Against Membrane Failure in Acute Ischemic Brain