Antinociceptive effect of d-Lys2, Dab4N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog

Abstract

BackgroundA 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. MethodsThe influence of cUP-1 (0.5–2mgkg−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 8mgkg−1, iv) on locomotor activity, motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement. ResultsAdministration of cUP-1 in doses of 1 and 2mgkg−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 (2mgkg−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. ConclusionsSystemic 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.