N^α-Methylhistamine Safety and Efficacy in Migraine Prophylaxis: Phase I and Phase II Studies.

Studies the therapeutic potential of the subcutaneous administration of N^α-methylhistamine in migraine prophylaxis. The histamine catabolite, N^α-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. Phase I.--In a clinical trial of 30 healthy volunteers, the effects of the subcutaneous administration of N^α-methylhistamine and placebo were studied to assess undesirable symptomatic effects. Phase II.--In a clinical open study, we evaluated the efficacy of N^α-methylhistamine in reducing headache intensity, frequency, and duration; and in decreasing analgesic intake in 18 patients with migraine. 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.--N^α-methylhistamine, at doses of 1 to 3 ng, significantly reduced (P<.0001) the frequency, intensity, and duration of migraine attacks. The present study provides evidence of the safety and efficacy of N^α-methylhistamine. (PsycInfo Database Record (c) 2021 APA, all rights reserved)