N^α-Methyl Histamine Safety and Efficacy in Migraine Prophylaxis: Phase III Study

Abstract

BACKGROUND: The histamine catabolite, Nalpha-methylhistamine, possesses a selective affinity for H3 receptors. For this reason, we considered evaluating the efficacy of this histaminergic H3 agonist in migraine prophylactic treatment. OBJECTIVE: To study the therapeutic potential of the subcutaneous administration of Nalpha-methylhistamine in migraine prophylaxis, in a Phase III clinical pharmacological study. METHODS: Using a controlled double-blind, placebo controlled clinical trial for 12 weeks, 60 patients with migraine, who fit the criteria established by the International Headache Society, were selected. The efficacy of subcutaneous administration of Nalpha-methylhistamine 1 to 3 ng twice a week against placebo was studied, evaluating the outcome of headache intensity, frequency, duration, and analgesic intake. RESULTS: Comparison between the groups treated with placebo (n=30) and Nalpha-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment, revealed that Nalpha-methylhistamine exerted a significant (p<0.0001) reduction (compared to placebo) in intensity, frequency, and duration of migraine attacks, as well as on the use of analgesic intake. No significant (p>0.05) adverse experiences or side effects developed in either group. CONCLUSIONS: The present study provides evidence of the efficacy of Nalpha-methylhistamine, given subcutaneously at doses of 1 to 3 ng twice a week, offering a new therapeutic alternative and laying the clinical and pharmacological groundwork for the use of histaminergic H3-agonists in migraine prophylaxis, which may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.