Abstract
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.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Animals
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Antihypertensive Agents / pharmacology*
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Blood Pressure / drug effects
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Blood Pressure / physiology
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Brain / blood supply
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Brain Damage, Chronic / physiopathology*
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Brain Ischemia / physiopathology*
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Male
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Pyrrolidines / pharmacology*
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Rats
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Rats, Wistar
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Receptors, Opioid, kappa / drug effects*
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Receptors, Opioid, kappa / physiology
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Regional Blood Flow / drug effects
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Regional Blood Flow / physiology
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Sodium-Potassium-Exchanging ATPase / drug effects
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Sodium-Potassium-Exchanging ATPase / physiology
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Synaptic Membranes / drug effects*
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Synaptic Membranes / physiology
Substances
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Antihypertensive Agents
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Pyrrolidines
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Receptors, Opioid, kappa
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Sodium-Potassium-Exchanging ATPase