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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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Novel peptide calcitonin gene-related peptide antagonists for migraine therapy.pdf - Published Version Available under License Creative Commons Attribution. Download (681kB) | Preview |
Abstract
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 |
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| 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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