WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Calcitonin gene-related peptide 
(CGRP) was first described as a potent vasodilator. * CGRP is also increasingly 
recognized as a key player in the pathophysiology of migraine, and CGRP receptor 
antagonists potentially offer a new approach for treating migraine. * A novel 
pharmacodynamic assay to measure CGRP receptor antagonist activity 
non-invasively in humans has been developed, which involves measuring the 
increase in dermal blood flow induced by topical application of capsaicin on the 
forearm.
WHAT THIS STUDY ADDS: * This study shows that the novel oral CGRP receptor 
antagonist, telcagepant, inhibits the increases in dermal blood flow induced by 
the topical application of capsaicin on the human forearm. * This experimental 
medicine model may have utility to assist in dose selection for the development 
of CGRP receptor antagonists.
AIMS: To evaluate inhibition of capsaicin-induced increase in dermal blood flow 
(DBF) following telcagepant (MK-0974), a potent and selective orally 
bioavailable calcitonin gene-related peptide (CGRP) receptor antagonist being 
developed for the acute treatment of migraine.
METHODS: A three-period crossover study in 12 healthy adult men. Each subject 
received a single oral dose of telcagepant 300 mg, telcagepant 800 mg or placebo 
at 0 h, followed 0.5 and 3.5 h later by two topical doses of 300 and 1000 microg 
capsaicin per 20 microl water-ethanol mixture. Capsaicin was applied at two 
sites on the volar surface of the subjects' left and right forearms. DBF was 
assessed by laser Doppler perfusion imaging immediately before ('baseline'), and 
0.5 h after each capsaicin application at 1 and 4 h. Plasma samples to determine 
telcagepant concentrations were collected immediately after laser Doppler 
perfusion imaging. A pharmacodynamic model was developed to explore the 
relationship between plasma concentration and inhibition of capsaicin-induced 
increase in DBF.
RESULTS: Geometric mean plasma concentrations after dosing with 300 mg and 800 
mg telcagepant were 720 and 1146 nm, respectively, at 1 h, vs. 582 and 2548 nm, 
respectively, at 4 h. The pharmacodynamic model suggested that the EC(90) for 
telcagepant inhibition of capsaicin-induced increases in DBF was 909 nm.
CONCLUSIONS: Telcagepant inhibits the increases in DBF induced by the topical 
application of capsaicin on the human forearm. This experimental medicine model 
may have utility to assist in dose selection for the development of CGRP 
receptor antagonists.