title: Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice.
abstract: The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kamei
authors.forename: A
authors.initials: A
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Ohsawa
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: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011804:Quinolines / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*
chemical_list: D000700:Analgesics; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67