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Potential protection by a specific kappa-opiate agonist U-50488H against membrane failure in acute ischemic brain.

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.
AuthorsT Furui
JournalNeurologia medico-chirurgica (Neurol Med Chir (Tokyo)) Vol. 33 Issue 3 Pg. 133-8 (Mar 1993) ISSN: 0470-8105 [Print] Japan
PMID7683118 (Publication Type: Journal Article)
Chemical References
  • Antihypertensive Agents
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Sodium-Potassium-Exchanging ATPase
Topics
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Blood Pressure (drug effects, physiology)
  • Brain (blood supply)
  • Brain Damage, Chronic (physiopathology)
  • Brain Ischemia (physiopathology)
  • Male
  • Pyrrolidines (pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, kappa (drug effects, physiology)
  • Regional Blood Flow (drug effects, physiology)
  • Sodium-Potassium-Exchanging ATPase (drug effects, physiology)
  • Synaptic Membranes (drug effects, physiology)

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