Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks

L H Lassen, M Ashina, I Christiansen, V Ulrich, R Grover, J Donaldson, J Olesen


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 received 546C88 (6 mg/kg) or placebo (5% dextrose) i.v. 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 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 involved in the pain mechanisms throughout the course of spontaneous migraine attacks.

Original languageEnglish
JournalCephalalgia : an international journal of headache
Issue number1
Pages (from-to)27-32
Number of pages6
Publication statusPublished - Jan 1998


  • Adolescent
  • Adult
  • Double-Blind Method
  • Enzyme Inhibitors/adverse effects
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Migraine Disorders/drug therapy
  • Nitric Oxide Synthase/antagonists & inhibitors
  • Treatment Outcome
  • omega-N-Methylarginine/adverse effects


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