Involvement of delta 1-opioid receptors in the antinociceptive effects of mexiletine in mice.
The mechanisms of the antinociceptive effect of mexiletine were assessed by administering selective mu-, delta- and kappa-opioid receptor antagonists in diabetic and non-diabetic mice. Intraperitoneal administration of mexiletine, at doses of 10 and 30 mg/kg, produced dose-dependent antinociception in the tail-pinch test in both non-diabetic and diabetic mice. The antinociceptive effect of mexiletine in diabetic mice was significantly greater than that in non-diabetic mice. The antinociceptive effect of mexiletine did not result from the activation of mu- or kappa-opioid receptors in either non-diabetic or diabetic mice, since treatment with either beta-funaltrexamine, a selective mu- opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was ineffective in blocking mexiletine-induced antinociception. The antinociceptive effect of mexiletine was significantly antagonized by naltrindole, a selective delta-opioid receptor antagonist, in both non-diabetic and diabetic mice. Furthermore, the antinociceptive effect of mexiletine was significantly reduced in both non-diabetic and diabetic mice following pretreatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, but not with naltriben, a selective delta 2-opioid receptor antagonist. These result suggest that delta 1-opioid receptor-mediated mechanisms may be involved in the antinociceptive effect of mexiletine.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Saitoh
A
A
Kasuya
Y
Y
D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D008297:Male; D008801:Mexiletine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012016:Reference Values
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D008801:Mexiletine; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole