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

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 hasbeen demonstrated. Given the existence of a relationship between the sigma systemand the kappa opioid (KOP)-mediated analgesia, to characterize thepharmacological properties of (+/-)-PPCC we analyzed its influence on theanalgesic effect of the systemic injected kappa agonist (-)-U-50,488H comparingthe effects with those shown by (+)-pentazocine and BD1047. The resultsdemonstrate that the systemic administration of (+/-)-PPCC (1 mg/kg s.c.) doesnot modify basal tail-flick latency. Pre-treatment with (+/-)-PPCC, at the samedose, significantly decreased the antinociceptive effect of (-)-U-50,488H,analogously to the sigma compounds used. This study confirms that (+/-)-PPCCplays the role of sigma agonist in this model and strengthens the hypothesis ofthe sigma receptor modulatory role on KOP-mediated analgesia.