title: Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries.
abstract: 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 microM 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 and 10 microM in most tissues. In contrast, telcagepant at concentrations up to 30 microM 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.
authors.affiliation: Departments of In Vivo Science, Merck Research Laboratories, West Point, PA 19486, USA. joseph_lynch@merck.com
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Regan
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Kane
mesh_terms: D000328:Adult; D001381:Azepines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D023303:Oxazolidinones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D014363:Tryptamines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; D023303:Oxazolidinones; D014363:Tryptamines; D014665:Vasodilator Agents; C089750:zolmitriptan; C525458:telcagepant