Vazegepant is the First Intranasal CGRP Receptor Antagonist for Migraine

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin peptide family. CGRP has two main forms (α And β). Specifically, CGRP is a highly effective vasodilator. It is important for physiological and pathological conditions including the cardiovascular system and wound healing. Besides, CGRP is mainly released from sensory nerves and is therefore related to pain pathways. Moreover, CGRP can mediate sympathetic outflow from the brain. CGRP may play a pathogenic role in the induction of migraine attacks. CGRP plays a role in gastrointestinal nociception, inflammation, gastric acid secretion, and motility. Furthermore, CGRP may play an important role in the function of the gut-brain microbial flora axis. In particular, treatments targeting CGRP or its receptors have shown efficacy as a preventive or acute treatment for migraine.

Meanwhile, COVID-19 is an acute respiratory disease caused by the RNA virus SARS-CoV-2. In severe cases, the infection can lead to pneumonia, severe acute respiratory syndrome, renal failure, and even death. Nonetheless, COVID-19 contains a coronal form of a spike protein that can attach to specific receptors present in epithelial cells and then reproduce. Here, we will introduce the first intranasal CGRP receptor antagonist for migraine, Vazegepant (BHV-3500).

Vazegepant is the First Intranasal CGRP Receptor Antagonist for Migraine.

First of all, Vazegepant (BHV-3500) is a high-affinity CGRP receptor antagonist (hCGRP Ki= 0.023 nM). Importantly, Vazegepant is the first intranasal medication for migraine. Particularly, Vazegepant may be helpful in the effective management of COVID-19-associated pulmonary inflammation.

In second place, Vazegepant is a fully competitive antagonist of CGRP receptors. Vazegepant binds to human CGRP receptors that are endogenous in SK-N-MC cell membranes, with an average Ki of 23+/- 2 pM.

Last but not the least, compared to adrenomedullin receptors 1 and 2, calcitonin and amyloid receptors 1 and 3, it has a selectivity for CGRP that exceeds 10000 times. Obviously, it shows a powerful and complete reversal of CGRP-induced dilation of isolated human intracranial arteries (EC50=880+/-50 pM).

All in all, Vazegepant (BHV-3500) is the first intranasal CGRP receptor antagonist for migraine.


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[2]  Mehta PP, et al. Am J Med Sci. 2021;361(5):557-566.

[3]  Health Psychol Res. 2022 Jun 28;10(3):35506.