Studies on analgesic oligopeptides. IV. Synthesis and analgesic activity of N-terminal shorter analogs of (D-Arg2)dermorphin and des-Tyr1-dermorphin analogs.

Abstract

Des-Tyr1-dermorphin, des-Tyr1-[D-Arg2] dermorphin, and the N-terminal di-, tri-, tetra- and hexapeptide amides of [D-Arg2] dermorphin were synthesized by a conventional solution method and their analgesic activities were assayed by means of the tail pressure test after subcutaneous administration (s. c.) to mice. The des-Tyr1 analogs of both dermorphin and [D-Arg2] dermorphin did not show analgesic activity even at a dose of up to 50 mg/kg, s. c. The N-terminal tetrapeptide amide, H-Tyr-D-Arg-Phe-Gly-NH2, showed extremely potent activity, being 31 times more active than morphine on a molar basis, whereas the N-terminal tri- and dipeptide amides showed no activity even at a dose of up to 40 mg/kg, s. c.