Nα-Methylhistamine Safety and Efficacy in Migraine Prophylaxis: Phase I and Phase II Studies
Background.—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.
Methods.—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.
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.—N α-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 N α-methylhistamine applied subcutaneously at doses of 1 to 3 ng twice a week.
Document Type: Research Article
Affiliations: 1: Department of Neurology, Unidad de Investigación Médica en Epidemiología Clínica, Hospital General de Zona UMF No 1 IMSS 2: Unidad de Investigación en Servicios de Salud, Cuauhtémoc IMSS 3: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Mexico.
Publication date: April 1, 2003