Analgesic and other pharmacological activities of an enkephalin analogue, syndyphalin (SD)-25.

The pharmacological actions of Tyr-D-Met(O)-Gly-MePheol (syndyphalin (SD)-25) were compared with those of morphine after systemic administration. The analgesic potency of SD-25 was about 4 times that of morphine when administered s.c. to rats. SD-25 did not exhibit any narcotic antagonist activity. Subcutaneous administration of SD-25 produced a dose-dependent suppression of morphine withdrawal signs in morphine-dependent rats, typical morphine-like jumping in the mouse jumping test, and an increase in spontaneous locomotor activity in mice. These activities were 2-5 times those of morphine. In the anaesthetized dog, intravenous administration of SD-25 produced a 100-1000 times stronger increase in the amplitude of contractions of the jejunum than did morphine, a weaker depression in respiration than morphine, and a slight increase in blood pressure. These effects were reversed by naloxone. These results indicate that SD-25 possesses potent central nervous system actions closely similar to those of morphine, but its effect on blood pressure and respiration was weaker than that of morphine.