The antinociceptive effect of leukotriene D4 receptor antagonist, MK- 571, in mice: Possible involvement of opioidergic mechanism

PubMed ID: 10618470The effect of a leukotriene D4 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 (ED50 = 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 (ED50 = 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.Celal Bayar ÜniversitesiThis study was supported by Research Foundation of Celal Bayar University. The authors wish to thank Merck Frosst for generously presenting MK-571. -