Nalpha-methyl histamine safety and efficacy in migraine prophylaxis: phase III study.

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.