Potential protection by a specific kappa-opiate agonist U-50488H against membrane failure in acute ischemic brain.
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.
Furui
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Department of Neurosurgery, Aichi Medical University.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects* / Q000502:physiology
D000959:Antihypertensive Agents; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000254:Sodium-Potassium-Exchanging ATPase