Effects of a selective sigma 1 antagonist compound on inflammatory pain.

Abstract

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.

• Authors: Carmela Parenti, Agostino Marrazzo, Giuseppina Aricò, Giuseppina Cantarella, Orazio Prezzavento, Simone Ronsisvalle, Giovanna Maria Scoto, Giuseppe Ronsisvalle
• Journal: Inflammation (Inflammation) Vol. 37 Issue 1 Pg. 261-6 (Feb 2014) ISSN: 1573-2576 [Electronic] United States
• PMID: 24049016 (Publication Type: Journal Article)

Chemical References

• Cyclopropanes
• Receptors, sigma
• cyclopropanecarboxylic acid
• Nitric Oxide
• Carrageenan
• Nitric Oxide Synthase

Topics

• Animals
• Carrageenan
• Cyclopropanes (pharmacology)
• Disease Models, Animal
• Edema (chemically induced, drug therapy)
• Hyperalgesia (chemically induced, drug therapy)
• Inflammation (chemically induced, drug therapy)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (metabolism)
• Pain (chemically induced, drug therapy)
• Pain Measurement
• Rats
• Rats, Sprague-Dawley
• Receptors, sigma (antagonists & inhibitors)