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

TY - JOUR

T1 - Comparison of the Vasoconstrictor Effects of the Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Telcagepant (MK-0974) and Zolmitriptan in Human Isolated Coronary Arteries.

AU - Lynch, Joseph J

AU - Regan, Christopher P

AU - Edvinsson, Lars

AU - Hargreaves, Richard J

AU - Kane, Stefanie A

PY - 2010

Y1 - 2010

N2 - 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 alphaCGRP, with the CGRP-mediated vasorelaxation completely blocked with 30 muM telcagepant. In coronary vessels at basal tone, zolmitriptan caused a concentration-dependent contraction (pEC50 = 6.9 +/- 0.1, slope 0.94), with the greatest contraction obtained between 1-10 muM in most tissues. In contrast, telcagepant at concentrations up to 30 muM 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.

AB - 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 alphaCGRP, with the CGRP-mediated vasorelaxation completely blocked with 30 muM telcagepant. In coronary vessels at basal tone, zolmitriptan caused a concentration-dependent contraction (pEC50 = 6.9 +/- 0.1, slope 0.94), with the greatest contraction obtained between 1-10 muM in most tissues. In contrast, telcagepant at concentrations up to 30 muM 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.

KW - coronary artery

KW - telcagepant

KW - zolmitriptan

U2 - 10.1097/FJC.0b013e3181d7665f

DO - 10.1097/FJC.0b013e3181d7665f

M3 - Article

C2 - 20164785

VL - 55

SP - 518

EP - 521

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 1533-4023

IS - 5

ER -