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Antinociceptive activity of (−)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid on acute pain in mice

Marinho, Bruno Guimarãesa; Miranda, Leandro S.M.b; Meireles, Bruno A.b; Vasconcellos, Mário L.A.A.c; Matheus, Maria E.a; Pereira, Vera L.P.b; Fernandes, Patricia D.a

doi: 10.1097/FBP.0b013e3283474a1b
ORIGINAL ARTICLES

Pain is a major cause of distress, both physical and psychological. There is a continuous search for new pharmacologically active analgesic agents with minor adverse effects. Recently, the synthesis of (−)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid [tetrahydropyran derivative (TD)] was described. The objective of this study was to investigate antinociceptive effects of TD. Its activity was compared with the activity of morphine. The effects of TD and morphine were evaluated in models of inflammatory and noninflammatory pain. TD (6–1200 μmol/kg, intraperitoneally) significantly reduced the nociceptive effects induced by acetic acid or formalin in mice. TD also demonstrated an antinociceptive effect in the tail-flick and hot-plate model. The opioid receptor antagonist, naloxone (at 15 μmol/kg, intraperitoneally), reversed the antinociceptive activity of TD in all the models evaluated. Morphine and TD induced tolerance in mice. However, the onset of tolerance to TD was delayed compared with that induced by morphine. These results indicate that TD develops significant antinociceptive activity and, at least part of its effects seems to be mediated by the opioid system.

aPharmacology of Inflammation and Nitric Oxide Laboratory, Institute of Biomedical Sciences, Federal University of Rio de Janeiro

bNucleus of Research of Natural Products, Stereoselective Synthesis of Bioactive Substances Laboratory, Federal University of Rio de Janeiro

cChemistry Department, Federal University of Paraíba, João Pessoa, Paraiba, Brazil

Correspondence to Dr Bruno Guimarães Marinho, DVM, MSc, PhD, Department of Physiological Sciences, Federal Rural University of Rio de Janeiro, Laboratory of Pharmacology, BR465, Km07, 23890-000, Seropédica, RJ, Brazil e-mail: bruno.marinho78@hotmail.com

Received June 12, 2010

Accepted March 3, 2011

© 2011 Lippincott Williams & Wilkins, Inc.