Results
Title

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF<sub>3</sub>-Phe-Asp]NH<sub>2</sub>.

Authors

Piekielna-Ciesielska, Justyna; Mollica, Adriano; Pieretti, Stefano; Fichna, Jakub; Szymaszkiewicz, Agata; Zielińska, Marta; Kordek, Radzisław; Janecka, Anna

Abstract

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH2 (C-36) and Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

Subjects

ANALGESICS; FLUORINATION; CYCLIC peptides; PHARMACODYNAMICS; ANTI-inflammatory agents; DRUG side effects

Publication

Journal of Enzyme Inhibition & Medicinal Chemistry, 2018, Vol 33, Issue 1, p560

ISSN

1475-6366

Publication type

Academic Journal

DOI

10.1080/14756366.2018.1441839