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

Abstract

The compound (1 R,2 S/1 S,2 R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropanecarboxylate [(±)-PPCC] is a ligand with high affinity for sigma (σ) sites of which the selectivity towards several other receptor systems has been demonstrated. Given the existence of a relationship between the σ 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 σ compounds used. This study confirms that (±)-PPCC plays the role of σ agonist in this model and strengthens the hypothesis of the σ receptor modulatory role on KOP-mediated analgesia.