Supraspinal delta 1-opioid receptor-mediated antinociceptive properties of (-)-TAN-67 in diabetic mice.
The antinociceptive potencies of the enantiomorphs of TAN-67 (2-methyl-4-alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4 a 5, 12, 12 a alpha-octahydroquinolino[2,3,3,-g]isoquinoline), (-)-TAN-67 and (+)-TAN-67, given intracerebroventricularly (i.c.v.) on the antinociceptive response were studied in streptozotocin-induced diabetic mice using the tail-flick test. (-)-TAN-67 at doses of 3-10 micrograms given i.c.v. produced dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice. The antinociceptive effect of (-)-TAN-67 in the tail-flick test in diabetic mice was greater than that in non-diabetic mice. 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, 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. On the other hand, in the tail-flick test. (+)-TAN-67 at doses of 3-30 micrograms given i.c.v. did not produce dose-dependent inhibition of the tail-flick response in either non-diabetic or diabetic mice. In conclusion, (-)-TAN-67, but not its enantiomer (+)-TAN-67, produced an antinociceptive effect through the activation of delta 1-opioid receptors.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. kamei@hoshi.ac.jp
Kawai
K
K
Mizusuna
A
A
Saitoh
A
A
Morita
K
K
Narita
M
M
Tseng
L F
LF
Nagase
H
H
D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism
D000700:Analgesics; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67