title: Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.
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.
authors.affiliation: MRC Cyclotron Unit and Department of Neurology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Gnecchi-Ruscone
authors.forename: X
authors.initials: X
authors.lastname: Bernard
authors.forename: P
authors.initials: P
authors.lastname: Pierre
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: N
authors.initials: N
authors.lastname: Legg
authors.forename: H
authors.initials: H
authors.lastname: Enahoro
authors.forename: P D
authors.initials: PD
authors.lastname: Winter
authors.forename: A
authors.initials: A
authors.lastname: Crisp
authors.forename: J A
authors.initials: JA
authors.lastname: Melin
authors.forename: P G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000328:Adult; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism*; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D014055:Tomography, Emission-Computed; D014363:Tryptamines; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D007211:Indoles; D010880:Piperidines; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C106783:naratriptan