@article{645202e42dcc403aa6ba5aabe3f6f99d,
title = "A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine",
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.",
keywords = "aCGRP (27-37), aCGRP (8-37), cAMP, plasma extravasation, SK-N-MC",
author = "\{von Mentzer\}, Bengt and Russo, \{Andrew F.\} and Zhongming Zhang and Adisa Kuburas and Killoran, \{Patrick M.\} and Vera D{\textquoteright}Aloisio and Laura Nizic and Vicky Capel and Kendall, \{David A.\} and Coxon, \{Christopher R.\} and Hutcheon, \{Gillian A.\}",
note = "Funding Information: The authors acknowledge Innovate UK (Biomedical Catalyst, Project number 132677) for funding towards the peptide stability and formulation studies and the NIH (NS075599) to AFR for plasma extravasation studies. Funding Information: The authors acknowledge Innovate UK (Biomedical Catalyst, Project number 132677) for funding towards the peptide stability and formulation studies and the NIH (NS075599) to AFR for plasma extravasation studies. AFR is a consultant for Alder Lundbeck Pharmaceuticals, Eli Lilly, Amgen, Novartis, Pharmnovo and Schedule One Therapeutics. DAK and BvM are Directors of Innovipharm Ltd. The authors acknowledge Innovate UK (Biomedical Catalyst, Project number 132677) for funding towards the peptide stability and formulation studies and the NIH (NS075599) to AFR for plasma extravasation studies. Capel, Coxon, Hutcheon, Kendall, Killoran and Metzer participated in research design. D?Aloisio, Killoran, Metzer, Nizic, Zhang and Russo conducted experiments. Capel, Coxon, D?Aloisio, Hutcheon, Kendall, Killoran, Metzer, Nizic and Kuburas performed data analysis. Coxon, Hutcheon, Kendall, Killoran, Metzer, Russo and Kuburas wrote or contributed to the writing of the manuscript. Publisher Copyright: {\textcopyright} 2020 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley \& Sons Ltd on behalf of Royal Pharmaceutical Society",
year = "2020",
month = jun,
day = "25",
doi = "10.1111/jphp.13317",
language = "English",
volume = "72",
pages = "1352--1360",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Oxford University Press",
number = "10",
}