Treatment of stroke with opiate antagonists - Effects of exogenous antagonists and dynorphin 1-13

D. S. Baskin, H. Kuroda, Y. Hosobuchi, N. M. Lee

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

We studied the effects of acute and long-term, continuous administration of six opioid compounds-naloxone, naltrexone, diprenorphine, leucine enkephalin, dynorphin 1-13, and dynorphin 3-13-on neurologic function, survival, and infarct size in a feline model of acute focal cerebral ischemia. Acutely, aaloxone, naltrexone, and diprenorphine significantly improved motor function over baseline scores; the other drugs and saline (control) had no effect. In the long-term condition, no substance administered significantly affected level of consciousness, sensory function, or pupillary reactions. Naloxone, naltrexone, and dynorphin 1-13 significantly prolonged survival (p<0.1); the other substances had no effect. Evaluations of cat brains postmortem showed that the infarcts involved the sensory and motor cortex, internal capsule, and caudate nucleus. Infarct size was unaltered by any treatment administered; results among groups were remarkably similar. In evaluations of opiate receptor binding characteristics, high-affinity binding of ekylketocyclozocine was significantly reduced in the right (occluded) side of the cortex. Dynorphin 1-13 given 8 h postocclusion but before sacrifice increased this binding affinity to the previous level in non-occluded cortex. The observed protective effect of dynorphin 1-13 warrants further investigation. Our results support the involvement of endogenous opioid peptides in the pathophysiology of cerebral ischemia and suggest that, administered appropriately, opiate antagonists may be useful in the treatment of focal ischemic neurologic deficits.

Original languageEnglish (US)
Pages (from-to)307-310
Number of pages4
JournalNeuropeptides
Volume5
Issue number4-6
DOIs
StatePublished - Feb 1985

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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