title: Antinociceptive effect of dihydroetorphine in diabetic mice.
abstract: The antinociceptive potency of dihydroetorphine in diabetic mice was examined. Subcutaneous administration of dihydroetorphine produced a dose-dependent antinociception in both non-diabetic and diabetic mice. The antinociceptive potency of s.c. dihydroetorphine was less in diabetic mice than in non-diabetic mice. The antinociception induced by i.c.v. dihydroetorphine (0.02 microgram) was also significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effects of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in non-diabetic mice, but not in diabetic mice, was also significantly antagonized by naloxonazine, a selective mu 1-opioid receptor antagonist. The time course and the potency of the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in diabetic mice were similar to those in naloxonazine-treated non-diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice. These results suggest that dihydroetorphine produces an antinociceptive effect through the activation of both mu 1- and mu 2-opioid receptors in mice. Furthermore, the reduction in dihydroetorphine-induced antinociception in diabetic mice, as compared with non-diabetic mice, may be due to the hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception in diabetic mice.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kamei
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Misawa
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: Y
authors.initials: Y
authors.lastname: Kasuya
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D010147:Pain Measurement; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D005048:Etorphine; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine; C055382:naltrindole; C034765:18,19-dihydroetorphine