CGRP receptor antagonists for migraine. Are they also AMY1 receptor antagonists?

The development of several drugs that target the calcitonin gene-related peptide (CGRP) system has been a major breakthrough in the pharmacological management of migraine. These are divided into two major classes, antibodies which bind to the CGRP peptide, preventing it from activating CGRP receptors and receptor antagonists. Within the receptor antagonist class, there are two mechanisms of action, small molecule receptor antagonists and an antibody antagonist. This mini-review considers the pharmacology of these receptor targeted antagonist drugs at the CGRP receptor and closely related AMY(1) receptor, at which CGRP may also act. The antagonists are most potent at the CGRP receptor but can also show antagonism of the AMY(1) receptor. However, important data are missing and selectivity parameters cannot be provided for all antagonists. The clinical implications of AMY(1) receptor antagonism are unknown, but we urge consideration of this receptor as a potential contributing factor to CGRP and antagonist drug actions.

Automated summary

The development of drugs targeting the CGRP system has been a major breakthrough in migraine management. These drugs can be classified into antibodies and receptor antagonists, with receptor antagonists further divided into small molecule antagonists and antibody antagonists. While antagonists are most potent at the CGRP receptor, they may also show antagonism at the AMY(1) receptor, indicating the need for further research.