Effects of a highly selective nonpeptide delta opioid receptor agonist, TAN-67, on morphine-induced antinociception in mice.
The effects of a potent and highly selective nonpeptide delta opioid receptor agonist, 2- methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha- octahydroquinolino [2,3,3,-g] isoquinoline (TAN-67), on morphine-induced antinociception were examined using the warm-plate (51 degrees C) method. When a peptide delta 1 opioid receptor agonist, [D-Pen2, Pen5]enkephalin (DPDPE), was co-administered with i.c.v. morphine, low-dose morphine-induced antinociception was significantly increased. In contrast, i.c.v. co-administration of a peptide delta 2 opioid receptor agonist, [D-Ala2]deltorphin II (DELT), with morphine did not affect the morphine-induced antinociception. When morphine and TAN-67 were co-administered i.c.v., low-dose morphine-induced antinociception was significantly increased. Moreover, when TAN-67 and morphine were co-administered s.c., the morphine dose-response curve shifted to the left and the ED50 value of morphine decreased. These effects DPDPE and TAN-67 were antagonized by the delta opioid receptor antagonist naltrindole (NTI) and the delta 1 opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) not by the delta 2 opioid receptor antagonist naltriben (NTB). Moreover, the mu opioid receptor antagonist beta-FNA also antagonized the effects of DPDPE and TAN-67. These results suggest that the effect of TAN-67 may result from the activation of central delta 1 opioid receptors, since the effect of TAN-67 was antagonized by NTI and BNTX, but not NTB. Furthermore, since pretreatment with beta-FNA also antagonized the effects of both DPDPE and TAN-67, a beta-FNA-sensitive site, i.e. a mu-delta complex site, may play an important role in the modulation of morphine-induced antinociception.
Suzuki
T
T
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Tsuji
M
M
Mori
T
T
Misawa
M
M
Endoh
T
T
Nagase
H
H
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000145:classification
D000700:Analgesics; D004745:Enkephalins; D009842:Oligopeptides; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-