A comparison of the antinociceptive and behavioral effects of D-Arg substituted dipeptides and tetrapeptides in mice.
Intracerebroventricular administration of D-Arg substituted dipeptides, H-Tyr-D-Arg-OMe and H-Tyr(Et)-D-Arg-OMe, and D-Arg2 substituted N-terminal tetrapeptides of dermorphin, H-Tyr-D-Arg-Phe-Gly-OEt and H-Tyr(Et)-D-Arg-Phe-Gly-OEt resulted in dose-related and naloxone-reversible antinociceptive effects. Among them, tetrapeptides not only exhibited much more potent and prolonged activities than dipeptides but also were significantly antagonized even by a low dose of naloxone. Spontaneous motor activity was lowered by dipeptides throughout the observation period, which was scarcely antagonized by naloxone. Tetrapeptides elicited locomotor hyperactivity following an initial locomotor suppression. Only the locomotor hyperactivity was significantly antagonized by naloxone. These results suggest that tetrapeptides induce the effects via opioid receptors, whereas the effects of dipeptides are involved in various systems non-specifically.
D000818:Animals; D001120:Arginine; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides; D010146:Pain / Q000503:physiopathology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D009294:Narcotics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D009020:Morphine; D001120:Arginine