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Novel peptide calcitonin gene-related peptide antagonists for migraine therapy.

Killoran, PM, Capel, V, D'Aloisio, V, Schofield, A, Aczél, T, Bölcskei, K, Helyes, Z, von Mentzer, B, Kendall, DA, Coxon, CR and Hutcheon, GA (2023) Novel peptide calcitonin gene-related peptide antagonists for migraine therapy. The Journal of pharmacy and pharmacology. pp. 1-9. ISSN 0022-3573

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Objectives It has previously been shown that the peptide (34Pro,35Phe)CGRP27-37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides. Methods Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies. Key findings A 10 amino acid-containing peptide VPTDVGPFAF-NH2 (P006) was identified as a key candidate to take forward for in vivo evaluation, where it was shown to be an effective antagonist after intraperitoneal injection into mice. P006 was formulated as a preparation suitable for nasal administration by spray drying with chitosan to form mucoadhesive microcarriers (9.55 ± 0.91 mm diameter) and a loading of 0.2 mg peptide per 20 mg dose.Conclusions The project has demonstrated the potential of these novel small peptide CGRP antagonists, to undergo future preclinical evaluation as anti-migraine therapeutics.

Item Type: Article
Uncontrolled Keywords: CGRP antagonist; chitosan microparticles; migraine; nasal delivery; peptide; 1115 Pharmacology and Pharmaceutical Sciences; 1116 Medical Physiology; Pharmacology & Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Oxford University Press
SWORD Depositor: A Symplectic
Date Deposited: 20 Nov 2023 16:59
Last Modified: 20 Nov 2023 17:00
DOI or ID number: 10.1093/jpp/rgad081
URI: https://researchonline.ljmu.ac.uk/id/eprint/21906
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