title: A new sigma ligand, (+/-)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Catania, Viale A. Doria, 6, 95125 Catania, Italy. prezzave@unict.it
authors.forename: Orazio
authors.initials: O
authors.lastname: Prezzavento
authors.forename: Carmela
authors.initials: C
authors.lastname: Parenti
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
authors.forename: Simone
authors.initials: S
authors.lastname: Ronsisvalle
authors.forename: Franco
authors.initials: F
authors.lastname: Vittorio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Aricò
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Scoto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ronsisvalle
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000378:metabolism; D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D003521:Cyclopropanes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000378:metabolism; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D010147:Pain Measurement; D010423:Pentazocine / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000700:Analgesics; D003521:Cyclopropanes; D005029:Ethylenediamines; D008024:Ligands; D010880:Piperidines; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; C518986:methyl 2-((4-hydroxy-4-phenylpiperidin-1-yl)methyl)-1-(4-methylphenyl)cyclopropanecarboxylate; C015766:cyclopropanecarboxylic acid; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010423:Pentazocine