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July 12, 2000; 55 (1) Article

Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs

T. Gnecchi–Ruscone, X. Bernard, P. Pierre, D. Anderson, N. Legg, H. Enahoro, P.D. O. Winter, A. Crisp, J.A. Melin, P.G. Camici
First published July 12, 2000, DOI: https://doi.org/10.1212/WNL.55.1.95
T. Gnecchi–Ruscone
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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X. Bernard
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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P. Pierre
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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D. Anderson
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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N. Legg
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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H. Enahoro
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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P.D. O. Winter
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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A. Crisp
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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J.A. Melin
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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P.G. Camici
From the MRC Cyclotron Unit and Department of Neurology (Drs. Gnecchi–RusconeAnderson, Legg, and Camici), Imperial College School of Medicine, Hammersmith Hospital, London, UK; Cyclotron Unit (Drs. Bernard, Pierre, and Melin), Université Catholique de Louvain, Belgium; and Glaxo Wellcome Neurology and Psychiatry Clinical Development (Drs. Bernard, Winter, Crisp, and H. Enahoro), Greenford, UK.
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Citation
Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs
T. Gnecchi–Ruscone, X. Bernard, P. Pierre, D. Anderson, N. Legg, H. Enahoro, P.D. O. Winter, A. Crisp, J.A. Melin, P.G. Camici
Neurology Jul 2000, 55 (1) 95-99; DOI: 10.1212/WNL.55.1.95

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Abstract

Background: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors.

Methods: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack.

Results: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (−13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo.

Conclusions: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

  • Received February 5, 1999.
  • Accepted in final form April 6, 2000.
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