Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.
OBJECTIVE
H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA.


METHODS
We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects.


RESULTS
[Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone.


CONCLUSIONS
Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.
Shimoyama
Megumi
M
Department of Anesthesiology, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan. shimoyama-teii@umin.ac.jp
Szeto
Hazel H
HH
Schiller
Peter W
PW
Tagaito
Yugo
Y
Tokairin
Hideyuki
H
Eun
Chong moon
Cm
Shimoyama
Naohito
N
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*
C424424:2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine