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Nα -Methyl Histamine Safety and Efficacy in Migraine Prophylaxis: Phase III Study

Published online by Cambridge University Press:  02 December 2014

Rebeca O. Millán-Guerrero ,
Rebeca Isais-Millán ,
Trujillo-Hernández Benjamín  and
Carlos E. Tene
Rebeca O. Millán-Guerrero*
Affiliation:
Department of Neurology, Unidad de Investigación Médica en Epidemiología, Clínica, Hospital General de Zona UMF No 1 IMSS. Colima
Rebeca Isais-Millán
Affiliation:
Medical student, ITESM., Campus Monterrey NL, México
Trujillo-Hernández Benjamín
Affiliation:
Department of Neurology, Unidad de Investigación Médica en Epidemiología, Clínica, Hospital General de Zona UMF No 1 IMSS. Colima
Carlos E. Tene
Affiliation:
Department of Neurology, Unidad de Investigación Médica en Epidemiología, Clínica, Hospital General de Zona UMF No 1 IMSS. Colima
*
J. Jesús Ponce No 538, Lomas de Circunvalación CP 28010, Colima, Col. México
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Abstract:

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Background:

The histamine catabolite, Nα-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 Nα-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 Nα-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 Nα-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment, revealed that Nα-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 Nα-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.

Résumé:

RÉSUMÉ: Contexte:

La Nμ-méthyle histamine, un catabolite de l’histamine, possède uneaffinité sélective pour les récepteurs H3. C’est la raison pour laquelle nous avons décidé d’évaluer l’efficacité de cetagonistehistaminergique H3 en prophylaxie de la migraine.

Objectif:

Étudier le potentielthérapeutique de l’administration souscutanée de Nμ-méthyle histamine en prophylaxie de la migraine dans un essaithérapeutique de phase III.

Méthodes:

Il s’agit d’une étude de 12 semainesà double insu, contrôlée par placebo, chez 60 patients migraineuxselon les critères établis par l‘International Headache Society. Nous avonsévalué l’effet de 1 à 3 ng de Nμ-méthyle histamine par voie sous-cutanée deuxfois par semainesur l’intensité, la fréquence et la durée de la céphalée ainsiquesur la prise d’analgésiques et nous l’avons comparé à l’effet d’un placebo.

Résultats:

L’analyse des données recueillies chez le grouperecevant le placebo (n = 30) et la Nμ-méthyle histamine (n = 30) à la quatrième, huitième et douzième semaine de traitement a montré que la Nμ-méthyle histamine diminuaitsignificativement l’intensité, la fréquence et la durée des accès de migraine ainsique la prise d‘analgésiques (p < 0,0001) par rapport au placebo. Aucun incident thérapeutique oueffetsecondairesignificatif n’a été observé dans l’un ou l’autre groupe (p < 0,05).

Conclusions:

Cette etude suggère que la Nμ-méthyle histamine à des doses de 1 à 3 ng par voie sous-cutanée deuxfois par semaineseraitefficace en prévention de la migraine, offrantainsiune nouvelle alternative thérapeutique. Elle établit les bases cliniques et pharmacologiques de l’utilisation d’agonistes histaminergiques H3 en prophylaxie de la migraine. Ces substances pourraientinhiberspécifiquement la réponse d’oedème neurogénique impliquée dans la physiopathologie de la migraine.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 33 , Issue 2 , May 2006 , pp. 195 - 199
Copyright
Copyright © The Canadian Journal of Neurological 2006

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