The antinociceptive effect of leukotriene D(4) receptor antagonist, MK-571, in mice: possible involvement of opioidergic mechanism.
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.
Gök
S
S
Department of Pharmacology, School of Medicine, Celal Bayar University, Manisa 45020, Turkey.
Onal
A
A
Cinar
M G
MG
Evinç
A
A
D015746:Abdominal Pain / Q000139:chemically induced / Q000517:prevention & control; D000085:Acetates; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D018077:Receptors, Leukotriene; D011957:Receptors, Opioid / Q000378:metabolism*
D000085:Acetates; D000700:Analgesics; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D009292:Narcotic Antagonists; D011422:Propionates; D011804:Quinolines; D018077:Receptors, Leukotriene; D011957:Receptors, Opioid; D009270:Naloxone; C059141:verlukast; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor