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CGRP receptor is a heterotrimer: a large peptide with 7 transmembrane domains, named calcitonin receptor-like receptor (CLR or CRLR), is supplemented by a small single transmembrane peptide, named receptor activity-modifying protein (RAMP1) that forms the CGRP-specific ligand binding site. CGRP receptors are expressed by multiple different cell types within the nervous, cardiovascular and immune systems that are thought to play important roles in migraine pathology: on cerebral vascular smooth muscle, where they cause vasodilation, on dural mast cells triggering their degranulation, at the central terminals of the trigeminal nerve, where CGRP is a neuromodulator at second-order nociceptive neurons in the spinal trigeminal nucleus caudalis and in the dorsal horn of the spinal cord, where CGRP has a similar role in inducing central sensitisation to tactile stimuli. CGRP is produced in both peripheral and central neurons. It is a potent peptide vasodilator and can function in the transmission of pain.

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Ubrogepant (MK-1602) is a novel potent, selective, oral calcitonin gene-related peptide receptor (CGRP) antagonist for acute treatment of migraine.




Atogepant is a potent, selective and orally available CGRP receptor antagonist for the prevention of migraine.




MK-8825 is a highly potent, selective, orally bioavailable CGRP receptor antagonist with Ki of 17 nM for rat CGRP; blocks hCGRP-stimulated cAMP responses in HEK293 cells stably expressing the human CGRP receptor with IC50 of 0.23 nM; possesses significantly improved in vivo potency in rat pharmacodynamic models.




MK-0974 is a potent, selective, orally bioavailable CGRP receptor antagonist with Ki of 0.77 nM; shows >10,000-fold selectivity in a panel of assays representing over 160 receptors, transporters, and enzymes; inhibits CGRP-stimulated cAMP production in E10 cells with IC50 of 2.2 nM; inhibits the capsaicin-induced increase in dermal blood flow in monkey models.

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