Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2

作者：Piekielna Ciesielska Justyna; Mollica Adriano; Pieretti Stefano; Fichna Jakub; Szymaszkiewicz Agata; Zielinska Marta; Kordek Radzislaw; Janecka Anna^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2018, 33(1): 560-566.

DOI：10.1080/14756366.2018.1441839

• Blood-brain barrier permeability
• hot-plate test
• anti-nociceptive and anti-inflammatory activity
• colitis induction
• myeloperoxidase activity

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.

• 出版日期2018-3-7