1. Naratriptan cardiac effects only “modest” among migraneurs
Nikhil Torsekar, Assistant Editor, Journal of American Medical Association
August 10, 2000
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British researchers examined the cardiac effects of the migraine treatment drug
naratriptan in a randomized, double-blind, placebo-controlled crossover trial, publishing
their findings in the July 12, 2000, issue of Neurology. Dr T. Gnecchi-Ruscone and
colleagues note that, despite extensive studies on adverse coronary events attributed to
the nonselective serotonin agonist ergotamine, little conclusive evidence exists about the
related effects of naratriptan. They acknowledge that the arterial constriction caused by
this selective serotonin analogue is localized to the brain, by virtue of its activity at only
5HT1 receptors. Nonetheless, they seek to further evaluate this mechanism with respect to
hyperemic myocardial blood flow and coronary vasodilator reserve, given “the small
population of 5HT1 receptors present on the vessel walls” of coronary arteries.
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Pharmacodynamic analysis was performed on 34 subjects at the Imperial College School
of Medicine in Great Britain, and the Université Catholique de Louvain in Belgium.
Participants were predominantly white (100%) and female (77%), ranged in age from 21
to 58 years, and met the International Headache Society criteria for migraine with or
without aura. The authors eliminated from consideration patients with ischemic heart
disease, atherosclerotic disease, basilar or hemiplegic migraine, severe cardiac
arrhythmias, high blood pressure, as well as those who were pregnant at the time of the
study. Concurrent use of ergotamine, sumatriptan, dihydroergotamine, methysergide,
lithium, and cardioactive medications were, similarly, considered grounds for exclusion
from the study. Additionally, one subject was removed from observation after
experiencing hypertension that constituted an ECG abnormality.
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Subject response to naratriptan was evaluated during 2 separate visits to the respective
Cyclotron Units of the British and Belgian centers. Three weeks after the initial

2. screening, each participant received a subcutaneous injection of naratriptan 1.5 mg and
placebo, in a sequence based upon their assigned randomized subject number. The
investigators used an intravenous infusion of PET with oxygen-15 labeled water and
dipyridamole, along with an ECAT 931-08/12 whole body positron scanner, to assess
both hyperemic and resting blood flow 3 weeks after injection. This diagnosis was
followed by additional observations made during a visit 5 days to 3 months later.
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Results corroborated previous clinical investigations indicating minimal cardiac effects
resulting from naratriptan administration. Myocardial blood flow was 13% lower for
patients treated with naratriptan versus placebo under hyperemic conditions (3.44 mL/
min/g vs. 3.97 mL/min/g), but nearly equal under resting conditions (1.14 mL/min/g vs.
1.16 mL/min/g). While comparable to placebo in its effects on coronary vasodilator
reserve, naratriptan produced a hyperemic coronary resistance that was 19% higher than
that of placebo (26.77 mm Hg X min/mL/g vs. 22.11 mm Hg X min/mL/g). Interestingly,
while 9 subjects experienced at least 1 adverse event (ie, headache and nausea) with
placebo, only 4 subjects in the naratriptan group voiced the same complaint. Although
patients in the naratriptan study were younger than those in the ergotamine study, the
authors found no age-related differences in the drugs’ effects on myocardial blood flow or
coronary vasodilator reserve.
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Gnecchi-Ruscone and colleagues note that their study underscores the ability of
naratriptan and other selective 5HT1B/1D agonists “to improve upon the safety of
nonselective serotonin agonists (eg, ergotamine), which are associated with…side effects
due to activity at multiple receptor types throughout the body.” They caution, however,
that the findings do not apply to patients with ischemic or coronary heart disease, and that
contraindications to selective serotonin agonists should be heeded.
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Neurology 2000:55;95-99