Beneficial effects of the kappa opioid receptor agonist U-50488H in experimental acute brain and spinal cord injury.

Abstract

The effects of the selective kappa opioid receptor agonist U-50488H (trans-3,4-dichloro-N-methyl-N[2-(pyrrolidinyl)-cyclohexyl]- benzeneacetamide) were examined in acute head and spinal injury models. First, in a blinded protocol, male CF-1 mice were treated intravenously with either saline or U-50488H (1, 3 or 10 mg/kg) within 3-5 min following a reproducible and quantifiable moderately severe (900 g/cm) concussive head injury. Using a grip test at 1 h postinjury to evaluate the neurological status of the injured mice, U-50488H produced a dose-related improvement in early recovery compared to the saline-treated mice. The effect was significant (P less than 0.05) after the 3 or 10 mg/kg i.v. doses. A similar concussive injury markedly reduced the % of cardiac output perfusing the forebrain (cerebral blood flow). U-50488H (10 and 20 mg/kg) partially reversed this effect to a significant degree 60 min after a 20 mg/kg dose. Secondly, the effects of U-50488H on the development of progressive post-traumatic spinal cord white matter ischemia after a 500 g/cm contusive injury were studied in pentobarbital-anesthetized cats. In 4 untreated cats, there was a progressive fall in spinal cord and blood flow (SCBF) from a 10-min postinjury level of 10.5 +/- 0.7 ml/100 g/min to 6.1 +/- 0.3 (P less than 0.03 by paired t at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: E D Hall, D L Wolf, J S Althaus, P F Von Voigtlander
• Journal: Brain research (Brain Res) Vol. 435 Issue 1-2 Pg. 174-80 (Dec 01 1987) ISSN: 0006-8993 [Print] Netherlands
• PMID: 2827851 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Pyrrolidines
• Receptors, Opioid
• Receptors, Opioid, kappa
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• Analgesics (therapeutic use)
• Animals
• Blood Pressure (drug effects)
• Brain Injuries (prevention & control)
• Cats
• Cerebrovascular Circulation (drug effects)
• Female
• Male
• Mice
• Pyrrolidines (pharmacology, therapeutic use)
• Receptors, Opioid (drug effects, physiology)
• Receptors, Opioid, kappa
• Regional Blood Flow (drug effects)
• Spinal Cord (blood supply)
• Spinal Cord Injuries (prevention & control)