Effects of a selective sigma 1 antagonist compound on inflammatory pain.
The compound (−)-MRV3 [(−)-Methyl (1S,2R)-2-[(4-Hydroxy-4-phenylpiperidin-1-yl)-methyl]-1-phenylcyclopropanecarboxylate] has an assessed antagonistsigma 1 (σ1) profile and showed improved σ1/σ2 selectivity with respect to the parent compound(+)-MR200. The σ1 receptor is reported to play arole in both central sensitization and pain hypersensitivity,which suggests a potential use of σ1 antagonists forthe treatment of persistent pain conditions. The present study was performed to assess the effects of theselective σ1 antagonist (−)-MRV3, in carrageenan-inducedinflammatory hyperalgesia, allodynia and edema.Mechanical allodynia with a series of calibratedvon Frey’s filaments, thermal hyperalgesia with plantartest and edema evaluation with a plethysmometerwere measured. Subcutaneous (s.c.) treatment with(−)-MRV3 (1, 2, 3, 4, 5 mg/kg) dose-dependentlyreduced allodynia and hyperalgesia induced byintraplantar carageenan. Furthermore, treatment with(−)-MRV3 (3 mg/kg s.c.) also inhibited paw edemawith a significant inhibition of 61.53 % 3 h aftercarrageenan treatment [corrected]. These results provide a strongbasis for the use of σ1 receptor antagonists in thetreatment of inflammatory pain.
Department of Drug Sciences, Pharmacology and Toxicology Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Carmela
C
Parenti
Agostino
A
Marrazzo
Giuseppina
G
Aricò
Giuseppina
G
Cantarella
Orazio
O
Prezzavento
Simone
S
Ronsisvalle
Giovanna Maria
GM
Scoto
Giuseppe
G
Ronsisvalle
D000818:Animals; D002351:Carrageenan; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*
D003521:Cyclopropanes; D017480:Receptors, sigma; C015766:cyclopropanecarboxylic acid; D009569:Nitric Oxide; D002351:Carrageenan; D019001:Nitric Oxide Synthase