A new sigma ligand, (+/-)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect

Life Sci. 2008 Mar 12;82(11-12):549-53. doi: 10.1016/j.lfs.2007.11.032. Epub 2008 Jan 11.

Abstract

The compound (1R,2S/1S,2R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropanecarboxylate [(+/-)-PPCC] is a ligand with high affinity for sigma (sigma) sites of which the selectivity towards several other receptor systems has been demonstrated. Given the existence of a relationship between the sigma system and the kappa opioid (KOP)-mediated analgesia, to characterize the pharmacological properties of (+/-)-PPCC we analyzed its influence on the analgesic effect of the systemic injected kappa agonist (-)-U-50,488H comparing the effects with those shown by (+)-pentazocine and BD1047. The results demonstrate that the systemic administration of (+/-)-PPCC (1 mg/kg s.c.) does not modify basal tail-flick latency. Pre-treatment with (+/-)-PPCC, at the same dose, significantly decreased the antinociceptive effect of (-)-U-50,488H, analogously to the sigma compounds used. This study confirms that (+/-)-PPCC plays the role of sigma agonist in this model and strengthens the hypothesis of the sigma receptor modulatory role on KOP-mediated analgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / metabolism
  • Analgesics / metabolism*
  • Animals
  • Cyclopropanes / chemistry*
  • Cyclopropanes / metabolism*
  • Cyclopropanes / pharmacology
  • Dose-Response Relationship, Drug
  • Ethylenediamines / metabolism
  • Ligands
  • Male
  • Molecular Structure
  • Pain Measurement
  • Pentazocine / metabolism
  • Piperidines / chemistry*
  • Piperidines / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / metabolism*

Substances

  • Analgesics
  • Cyclopropanes
  • Ethylenediamines
  • Ligands
  • Piperidines
  • Receptors, Opioid, kappa
  • Receptors, sigma
  • methyl 2-((4-hydroxy-4-phenylpiperidin-1-yl)methyl)-1-(4-methylphenyl)cyclopropanecarboxylate
  • cyclopropanecarboxylic acid
  • N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Pentazocine