Antinociceptive effect of d-Lys2,Dab4 N-(ureidoethyl)amide,a new cyclic 1-4 dermorphin/deltorphin analog

Background a preliminary evaluation of antinociceptive activity of a new cyclic dermorphin/deltorphin tetrapeptide analog restricted via a urea bridge and containing c-terminal ureidoethylamid {[h-tyr-d-lys(&1)-phe- dab(&2)-ch2ch2nhconh2] [&1co&2]} (cup-1) revealed a significant and long-lasting increase of pain threshold to thermal stimulation after systemic application. the current studies were aimed at further evaluation of cup-1 activity in animal models of somatic and visceral pain. the influence of cup-1 on motor functions was also investigated. methods the influence of cup-1 (0.5-2 mg kg-1,iv) on nociceptive threshold to mechanical pressure and analgesic efficacy in formalin and acetic acid-induced writhing tests were estimated. the antinociceptive effect of cup-1 was compared to that of morphine (mf). the influence of cup-1 (1,4 and 8 mg kg-1,iv) on locomotor activity,motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement. results administration of cup-1 in doses of 1 and 2 mg kg-1 elicited a significant increase of nociceptive threshold to mechanical pressure. mf applied in the same doses induced an antinociceptive effect only at the higher dose (2 mg kg -1). there were no marked differences between the effect of cup-1 and mf at each dose,at relative time points. in the writhing test and both phases of the formalin test,cup-1 showed a significant,dose-dependent antinociceptive effect which did not markedly differ from that of mf. cup-1 did not significantly affect motor functions of mice. conclusions systemic application of cup-1 elicited a dose-dependent antinociceptive effect. the analgesic efficacy of cup-1 on mechanical nociception,visceral and formalin-induced pain was comparable to that of mf. cup-1 did not impair motor functions of mice. © 2014 institute of pharmacology,polish academy of sciences.