piperidines and cyclopropanecarboxylic-acid

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.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Cyclopropanes; Dose-Response Relationship, Drug; Ethylenediamines; Ligands; Male; Molecular Structure; Pain Measurement; Pentazocine; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, sigma