The antinociceptive effect of leukotriene D(4) receptor antagonist, MK-571, in mice: possible involvement of opioidergic mechanism

Eur J Pharmacol. 1999 Dec 15;386(2-3):195-200. doi: 10.1016/s0014-2999(99)00756-6.

Abstract

The effect of a leukotriene D(4) receptor antagonist, (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl(3-dimethyl amino-3-oxo propyl)thio)methyl)thio) propanoic acid (L-660,711; MK-571), was investigated on nociceptive responses in mice using three different assays: acetic-acid-induced abdominal constrictions, formalin response and tail-flick test. MK-571 (8-32 mg/kg, i.v.) produced dose-dependent protection against acetic-acid-induced abdominal constriction (ED(50)=30 mg/kg). The compound (10-80 mg/kg, i.p.) was also effective, in a dose-dependent manner, on the second phase of the formalin response (ED(50)=26 mg/kg). However, it had no effect on the first phase of the formalin response and in the tail-flick test. Naloxone (1 mg/kg, i.v.), an opioid antagonist, almost completely blocked the antinociceptive effect of MK-571 in both acetic-acid-induced abdominal constriction and the second phase of the formalin test. These results provide evidence for an antinociceptive action of MK-571 at peripheral sites and suggest that opioid mechanisms are involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / chemically induced
  • Abdominal Pain / prevention & control
  • Acetates
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Body Temperature / drug effects
  • Leukotriene Antagonists* / pharmacology*
  • Leukotriene Antagonists* / therapeutic use
  • Male
  • Membrane Proteins*
  • Mice
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain Measurement / drug effects
  • Propionates / pharmacology*
  • Propionates / therapeutic use
  • Quinolines / pharmacology*
  • Quinolines / therapeutic use
  • Receptors, Leukotriene*
  • Receptors, Opioid / metabolism*

Substances

  • Acetates
  • Analgesics
  • Leukotriene Antagonists
  • Membrane Proteins
  • Narcotic Antagonists
  • Propionates
  • Quinolines
  • Receptors, Leukotriene
  • Receptors, Opioid
  • Naloxone
  • verlukast
  • cysteinyl leukotriene receptor 2
  • leukotriene D4 receptor