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Keywords:

  • Nα-methylhistamine;
  • H3 receptors;
  • safety and efficacy;
  • migraine prophylaxis;
  • pathophysiology

Objective.—To study the therapeutic potential of the subcutaneous administration of Nα-methylhistamine in migraine prophylaxis.

Background.—The histamine catabolite, Nα-methylhistamine, possesses a selective affinity for H3 receptors. We consequently considered it viable to conduct a clinical pharmacological study to evaluate the safety and efficacy of this histaminergic H3 agonist in migraine prophylactic treatment, which specifically may inhibit the neurogenic edema response involved in migraine pathophysiology.

Methods.—Phase I.—In a clinical trial of 30 healthy volunteers, the effects of the subcutaneous administration of Nα-methylhistamine and placebo were studied to assess undesirable symptomatic effects.

Phase II.—In a clinical open study, we evaluated the efficacy of Nα-methylhistamine in reducing headache intensity, frequency, and duration; and in decreasing analgesic intake in 18 patients with migraine.

Results.—Phase I.—None of the variables studied showed significant differences (P>.05), and no secondary effects were observed at doses below 10 ng.

Phase II.—Nα-methylhistamine, at doses of 1 to 3 ng, significantly reduced (P<.0001) the frequency, intensity, and duration of migraine attacks, as well as the need for rescue analgesics. However, at doses greater than 3 ng, patients experienced intense headache.

Conclusions.—The present study provides evidence of the safety and efficacy of Nα-methylhistamine applied subcutaneously at doses of 1 to 3 ng twice a week.