verlukast and Abdominal-Pain

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.

Topics: Abdominal Pain; Acetates; Analgesics; Animals; Body Temperature; Leukotriene Antagonists; Male; Membrane Proteins; Mice; Naloxone; Narcotic Antagonists; Pain Measurement; Propionates; Quinolines; Receptors, Leukotriene; Receptors, Opioid