Comparison of the Vasoconstrictor Effects of the Calcitonin Gene-related Peptide Receptor Antagonist Telcagepant (MK-0974) and Zolmitriptan in Human Isolated Coronary Arteries

Studies were conducted in human isolated coronary arteries to explore the vascular effects of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant and to compare its coronary vasoconstrictive potential to that of zolmitriptan. KCl precontracted coronary vessels were shown to relax to human alpha CGRP, with the CGRP-mediated vasorelaxation completely blocked with 30 mu M telcagepant. In coronary vessels at basal tone, zolmitriptan caused a concentration-dependent contraction (pEC(50) = 6.9 +/- 0.1; slope 0.94), with the greatest contraction obtained between 1 and 10 mu M in most tissues. In contrast, telcagepant at concentrations up to 30 mu M evoked no change in contractile tone. These findings suggest the potential for CGRP receptor antagonists to exert antimigraine efficacy in the absence of adverse effects on coronary tone.