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.