Comparison of opioid activity between a N-terminal tetrapeptide analogue of dermorphin, H-Tyr-D-Arg-Phe-beta-Ala-OH and morphine.
The antinociceptive properties of dermorphin tetrapeptide analog, H-Tyr-D-Arg-Phe-beta-Ala-OH (TDAPA) were compared with morphine in mice. In the tail-pressure test, subcutaneously (s.c.) injected TDAPA and morphine produced significant antinociceptive activity. Pretreatment with naloxonazine (35 mg/kg, s.c., 24 h before testing) significantly antagonized the activity induced by TDAPA, but not morphine. The ED50 values of TDAPA changed from 0.39 mg/kg to 1.7 mg/kg by naloxonazine pretreatment In the formalin test, both TDAPA and morphine exhibited dose-related antinociceptive activity with ED50 values of 0.49 mg/kg and 2.5 mg/kg, respectively. Both drug activities were significantly antagonized by naloxonazine. These results indicate different mechanisms of action for TDAPA and morphine, suggesting TDAPA is highly selective for the mu 1-opioid receptor and may be clinically useful.
Sato
T
T
Department of Pharmaceutics, Tohoku College of Pharmacy, Sendai, Japan.
Takahashi
N
N
Tan-No
K
K
Kisara
K
K
Sakurada
T
T
Sakurada
S
S
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides; D010147:Pain Measurement / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin; D009020:Morphine; C059394:tyrosyl-arginyl-phenylalanyl-alanine