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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland

    Bożena Antkowiak, Małgorzata Paluch, Magdalena Ciechanowska, Małgorzata Nawrocka, Janusz Kocik & Marek Kowalczyk

  2. Pharmaceutical Research Institute, Warsaw, Poland

    Krzysztof Bańkowski & Olga Michalak

  3. Józef Piłsudski University of Physical Education, Warsaw, Poland

    Marek Kowalczyk

  4. Department of Chemistry, Warsaw University, Warsaw, Poland

    Jan Izdebski

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  1. Bożena Antkowiak
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  2. Małgorzata Paluch
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Antkowiak, B., Paluch, M., Ciechanowska, M. et al. Antinociceptive effect of d-Lys2, Dab4 N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog. Pharmacol. Rep 66, 600–605 (2014). https://doi.org/10.1016/j.pharep.2014.01.007

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