An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice. Issue 14 (1st August 2018)

• Record Type: Journal Article
• Authors: Skogh, Anna; Lesniak, Anna; Sköld, Christian; Karlgren, Maria; Gaugaz, Fabienne Z.; Svensson, Richard; Diwakarla, Shanti; Jonsson, Anna; Fransson, Rebecca; Nyberg, Fred; Hallberg, Mathias; Sandström, Anja
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 14(2018)
• Page Start: 2446
• Page End: 2450
• Publication Date: 2018-08-01
• Subjects: Substance P 1–7 -- Peptidomimetics -- Neuropathic pain -- SNI mice -- Phenylalanine bioisostere; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.06.009
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The dipeptide amide H-Phe-Phe-NH2 (1 ) that previously was identified as a ligand for the substance P 1–7 (SP1–7 ) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1–7 and the tetrapeptide endomorphin-2 that is also binding to the SP1–7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4 ) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50 ) of4 was superior as compared to gabapentin and morphine that are used in clinic.