Nalpha-methyl histamine safety and efficacy in migraine prophylaxis: phase III study

Can J Neurol Sci. 2006 May;33(2):195-9. doi: 10.1017/s0317167100004960.


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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / metabolism
  • Cerebral Arteries / physiopathology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Histamine / metabolism
  • Histamine Agonists / administration & dosage*
  • Histamine Agonists / adverse effects
  • Humans
  • Injections, Subcutaneous
  • Male
  • Methylhistamines / administration & dosage*
  • Methylhistamines / adverse effects
  • Middle Aged
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / physiopathology
  • Migraine Disorders / prevention & control*
  • Placebos
  • Receptors, Histamine H3 / drug effects
  • Receptors, Histamine H3 / metabolism
  • Treatment Outcome


  • Analgesics
  • Histamine Agonists
  • Methylhistamines
  • Placebos
  • Receptors, Histamine H3
  • Histamine