[Migraine. Review of physiopathogeny and future alternative therapy]. / Migraña. Una revisión de la fisiopatogenia y alternativa terepéutica futura.

This work examines recent discoveries in physiopathogenesis, focusing on the combination of sequential events involved in migraine origin. Recent facts concerning active intestinal peptide, substance P, histamine, HI and H3 receptors, and H3-receptor agonists, all neuromodulators having an intimate relations ship with migraine were examined. Present-day recommended treatment, with an efficacy of barely 70%, and reasons for its poor performance were described. The authors state that the future of migraine treatment should be directed toward the search for drugs that directly interact with the above-mentioned neuromodulators, thus offering patients a more efficacious treatment and fewer undesirable side-effects.

Nalpha-methylhistamine safety and efficacy in migraine prophylaxis: phase I and phase II studies.

OBJECTIVE: To study the therapeutic potential of the subcutaneous administration of Nalpha-methylhistamine in migraine prophylaxis. BACKGROUND: The histamine catabolite, Nalpha-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 Nalpha-methylhistamine and placebo were studied to assess undesirable symptomatic effects. Phase II.-In a clinical open study, we evaluated the efficacy of Nalpha-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.-Nalpha-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 Nalpha-methylhistamine applied subcutaneously at doses of 1 to 3 ng twice a week.