Antinociceptive effects of [D-Ala2]deltorphin II, a highly selective delta agonist in vivo.
The present study has characterized the antinociceptive actions of [D-Ala2]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala2]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala2]deltorphin II was 13-fold more potent than i.c.v. [D-Pen2, D-Pen5]enkephalin (DPDPE), a second highly selective delta agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala2]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective delta antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium mu antagonist, beta-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala2]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala2]deltorphin II produced its antinociceptive effects at a supraspinal delta receptor. [D-Ala2]deltorphin II appears to be the most appropriate delta opioid agonist currently available for studies in vivo and support the involvement of delta receptors in supraspinal antinociception.
Qi
J A
JA
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Mosberg
H I
HI
Porreca
F
F
D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine