Antinociceptive effect of D-Lys(2), Dab(4) N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog

作者：Antkowiak Bozena^*; Paluch Malgorzata; Ciechanowska Magdalena; Nawrocka Malgorzata; Bankowski Krzysztof; Michalak Olga; Kocik Janusz; Kowalczyk Marek; Izdebski Jan

来源：Pharmacological Reports, 2014, 66(4): 600-605.

DOI：10.1016/j.pharep.2014.01.007

• Dermorphin
• Deltorphins
• Ureidopeptide
• Opioid peptide
• Antinociception

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][&(CO)-C-1&(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.

• 出版日期2014-8