Migraine is a disabling neurological disorder with symptoms that can last for days and is commonly underdiagnosed, and many sufferers do not receive appropriate therapy. In this issue Salvatore et al. describe the preclinical pharmacological characterization of MK-3207 [2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-yl]acetamide], a novel, selective, potent, and orally bioavailable calcitonin gene-related peptide (CGRP) antagonist in the treatment of migraine. It is noteworthy that, due to the species selectivity of MK-3207, its potency was determined in a rhesus pharmacodynamic assay measuring capsaicin-induced dermal blood flow via Doppler imaging where MK-3207 demonstrates superior potency and efficacy relative to other CGRP antagonists. The superior preclinical properties of MK-3207 appear to translate into the clinic as encouraging phase II results have been observed for MK-3207 in the treatment of acute migraine. Although the exact mechanism linking CGRP and migraine has yet to be identified, clinical efficacy observed with the CGRP antagonists offers hope for migraine sufferers.
See article at J Pharmacol Exp Ther 2010, 333:152–160.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics