11 research outputs found
A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine
Objectives: To investigate the formulation of the peptideābased antagonist (34Pro,35Phe)CGRP27ā37, of the human calcitonin geneārelated 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 LCāMS. Antagonist potency was assessed by measuring CGRPāstimulated cAMP accumulation in SKāNāMC, 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. Peptideācontaining chitosan microparticles were prepared by spray drying.
Key findings: (34Pro,35Phe)CGRP27ā37 exhibited a 10āfold increased affinity compared to Ī±CGRP27ā37. Administration of (34Pro,35Phe)CGRP27ā37 to mice led to a significant decrease in CGRPāinduced PPE confirming antagonistic properties in vivo . There was no degradation of (34Pro,35Phe)CGRP27ā37 and no loss of antagonist potency during formulation and release from chitosan microparticles.
Conclusions: (34Pro,35Phe)CGRP27ā37 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 antiāmigraine medicine