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A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine

von Mentzer, B, Russo, AF, Zhang, Z, Kuburas, A, Killoran, PM, D'Aloisio, V, Nizic, L, Capel, V, Kendall, DA, Coxon, CR and Hutcheon, GA (2020) A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine. Journal of Pharmacy and Pharmacology. ISSN 0022-3573

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Abstract

Objectives: To investigate the formulation of the peptide‐based antagonist (34Pro,35Phe)CGRP27–37, of the human calcitonin gene‐related peptide (CGRP) receptor as a potential nasally delivered migraine treatment.
Methods: Peptide sequences were prepared using automated methods and purified by preparative HPLC. Their structure and stability were determined by LC‐MS. Antagonist potency was assessed by measuring CGRP‐stimulated cAMP accumulation in SK‐N‐MC, cells and in CHO cells overexpressing the human CGRP receptor. In vivo activity was tested in plasma protein extravasation (PPE) studies using Evans blue dye accumulation. Peptide‐containing chitosan microparticles were prepared by spray drying.
Key findings: (34Pro,35Phe)CGRP27–37 exhibited a 10‐fold increased affinity compared to αCGRP27–37. Administration of (34Pro,35Phe)CGRP27–37 to mice led to a significant decrease in CGRP‐induced PPE confirming antagonistic properties in vivo . There was no degradation of (34Pro,35Phe)CGRP27–37 and no loss of antagonist potency during formulation and release from chitosan microparticles.
Conclusions: (34Pro,35Phe)CGRP27–37 is a potent CGRP receptor antagonist both in vitro and in vivo, and it can be formulated as a dry powder with no loss of activity indicating its potential as a nasally formulated anti‐migraine medicine.

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology and Pharmaceutical Sciences, 1116 Medical Physiology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Related URLs:
Date Deposited: 07 Aug 2020 12:42
Last Modified: 07 Aug 2020 12:45
DOI or Identification number: 10.1111/jphp.13317
URI: http://researchonline.ljmu.ac.uk/id/eprint/13471

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