Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries

Joseph J Lynch; Christopher P Regan; Lars Edvinsson; Richard J Hargreaves; Stefanie A Kane

doi:10.1097/FJC.0b013e3181d7665f

Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries

Joseph J Lynch, Christopher P Regan, Lars Edvinsson, Richard J Hargreaves, Stefanie A Kane

18 Citations (Scopus)

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.

Original language	English
Journal	Journal of Cardiovascular Pharmacology
Volume	55
Issue number	5
Pages (from-to)	518-21
Number of pages	4
ISSN	0160-2446
DOIs	https://doi.org/10.1097/FJC.0b013e3181d7665f
Publication status	Published - May 2010
Externally published	Yes

Keywords

Adult
Azepines
Coronary Vessels
Dose-Response Relationship, Drug
Humans
Imidazoles
In Vitro Techniques
Middle Aged
Migraine Disorders
Oxazolidinones
Receptors, Calcitonin Gene-Related Peptide
Tryptamines
Vasoconstriction
Vasodilation
Vasodilator Agents

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Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries. / Lynch, Joseph J; Regan, Christopher P; Edvinsson, Lars et al.
In: Journal of Cardiovascular Pharmacology, Vol. 55, No. 5, 05.2010, p. 518-21.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.",

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author = "Lynch, {Joseph J} and Regan, {Christopher P} and Lars Edvinsson and Hargreaves, {Richard J} and Kane, {Stefanie A}",

year = "2010",

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T1 - Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide 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 - 2010/5

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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 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.

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 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.

KW - Adult

KW - Azepines

KW - Coronary Vessels

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Imidazoles

KW - In Vitro Techniques

KW - Middle Aged

KW - Migraine Disorders

KW - Oxazolidinones

KW - Receptors, Calcitonin Gene-Related Peptide

KW - Tryptamines

KW - Vasoconstriction

KW - Vasodilation

KW - Vasodilator Agents

U2 - 10.1097/FJC.0b013e3181d7665f

DO - 10.1097/FJC.0b013e3181d7665f

M3 - Journal article

C2 - 20164785

SN - 0160-2446

VL - 55

SP - 518

EP - 521

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

IS - 5

ER -

Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries

Abstract

Keywords

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