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

Background: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant red uction of hyperemic myocardial blood flow, but little is known about the ef fect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT(2) receptors. The s elective 5HT(1B/1D) agonist naratriptan has no significant activity at 5HT( 2) receptors; however, like all 5HT(1B/1D) agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary ar teries by activation of 5HT(1B) receptors. Methods: The effects on myocardi al blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 l abeled water during two separate visits. This study was a randomized, doubl e-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. Res ults: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall i n hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or sy mptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) com pared with placebo. Conclusions: These results show that at therapeutic dos es, naratriptan exerts only a minor effect on myocardial blood flow, corona ry vasodilator reserve, or coronary resistance among subjects with no evide nce of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT(1) agonists for migr aine are contraindicated.