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.
Millán-Guerrero
Rebeca O
RO
Department of Neurology, Unidad de Investigación Médica en Epidemiología Clínica, Hospital General de Zona UMF No 1 IMSS, Mexico.
Pineda-Lucatero
Alicia G
AG
Hernández-Benjamín
Trujillo
T
Tene
Carlos E
CE
Pacheco
Mauro F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D017442:Histamine Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008761:Methylhistamines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D011968:Receptors, Histamine / Q000378:metabolism; D016896:Treatment Outcome
D017442:Histamine Agonists; D008761:Methylhistamines; D011968:Receptors, Histamine; C069357:alpha-methylhistamine