NITRIC-OXIDE SYNTHASE INHIBITION - A NEW PRINCIPLE IN THE TREATMENT OF MIGRAINE ATTACKS

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histami ne, 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 th is question we studied the effect of L-N(G)methylarginine hydrochlorid e (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) iv given over 15 min for a single migraine attack (546C88:placebo, 15:3). Furth ermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the st atistical evaluation. Two hours after the infusion, 10 of 15 L-N(G)met hylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebo-treated 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 invol ved in the pain mechanisms throughout the course of spontaneous migrai ne attacks.