Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity.
In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor.
Horan
P
P
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Tallarida
R J
RJ
Haaseth
R C
RC
Matsunaga
T O
TO
Hruby
V J
VJ
Porreca
F
F
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta
D000700:Analgesics; D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D004744:Enkephalin, Methionine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-