Nitric Oxide Synthase Inhibition: A New Principle in the Treatment of Migraine Attacks

Author:

Lassen LH1,Ashina M1,Christiansen I1,Ulrich V1,Grover R2,Donaldson J2,Olesen J1

Affiliation:

1. Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark

2. Glaxo Wellcome Research and Development, Greenford, Middlesex, United Kingdom

Abstract

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly 546C88 (6 mg/ kg) or placebo (5% dextrose) iv given over 15 min for a single migraine attack (546C88: placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebotreated patients ( p=0.01). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.

Publisher

SAGE Publications

Subject

Clinical Neurology,General Medicine

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