Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that is widely expressed in the peripheral and central nervous system.  CGRP has been implicated as a key player in migraine pathogenesis and clinical studies have demonstrated that small molecule CGRP receptor antagonists are effective for the acute treatment of migraine.  The orally bioavailable clinical compounds telcagepant  and MK-3207  are both potent antagonists at the human CGRP receptor but they exhibit significantly lower affinity for non-primate CGRP receptors.  One consequence of this pronounced species selectivity is that such compounds are unattractive for use in rodent models because the high doses required would be impractical.  Nonetheless, the ability to evaluate small molecule CGRP receptor antagonists in rodent models should greatly facilitate efforts to elucidate the complex biology of CGRP.  We describe the identification and properties of MK-8825 , a potent and selective CGRP receptor antagonist with good oral activity in rats.

MK-8825: A potent and selective CGRP receptor antagonist with good oral activity in rats

243rd National Meeting (2012)

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