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.
Millán-Guerrero
Rebeca O
RO
Department of Neurology, Unidad de Investigación Medica en Epidemiología Clínica, Hospital General de Zona UMF No 1 IMSS. Colima.
Isais-Millán
Rebeca
R
Benjamín
Trujillo-Hernández
TH
Tene
Carlos E
CE
D000328:Adult; D000700:Analgesics / Q000008:administration & dosage; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008761:Methylhistamines / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D010919:Placebos; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D000700:Analgesics; D017442:Histamine Agonists; D008761:Methylhistamines; D010919:Placebos; D018100:Receptors, Histamine H3; D006632:Histamine