Novel strategies for the treatment of migraine attacks via the CGRP, serotonin, dopamine, PAC1, and NMDA receptors

Expert Opin Drug Metab Toxicol. 2014 Nov;10(11):1509-20. doi: 10.1517/17425255.2014.963554. Epub 2014 Sep 25.

Abstract

Introduction: Migraine is a common, paroxysmal, and disabling primary headache with a high personal and socioeconomic impact. It involves ∼ 16% of the general population. During the years, a number of hypotheses have been put forward concerning the exact pathomechanism, but the final solution is still undiscovered.

Areas covered: Although the origin is enigmatic, parallel therapeutic efforts have been developed. Current attack therapy does not meet the expectations of the patients or the doctors. This article, based on a PubMed search, reviews the novel pharmacological possibilities that influence the peripheral and central sensitization involved in the disease.

Expert opinion: In order to overcome the therapeutic insufficiency, a calcitonin gene-related peptide receptor antagonist without the side-effect of liver transaminase elevation is required. Another therapeutic option is to develop a neurally acting antimigraine agent, such as a serotonin-1F receptor agonist, with low adverse central nervous system events. Development of a potent dopamine receptor antagonist is necessary to diminish the premonitory symptoms of migraine. A further option is to decrease the headache intensity with a pituitary adenylate cyclase-activating polypeptide type 1 receptor blocker which can cross the blood-brain barrier. Finally, synthetic kynurenine analogues are required to block the pain transmission in the activated trigeminal system.

Keywords: 5-hydroxytryptamine 1F receptor agonist; N-methyl-D-aspartate receptor inhibitors; calcitonin gene-related peptide receptor antagonists; dopamine receptor antagonists; migraine attack therapy; pituitary adenylate cyclase-activating polypeptide type 1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Dopamine Antagonists / therapeutic use
  • Drug Design*
  • Humans
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / physiopathology
  • Receptor, Serotonin, 5-HT1F
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / antagonists & inhibitors
  • Receptors, Serotonin / drug effects
  • Serotonin Receptor Agonists / pharmacology
  • Serotonin Receptor Agonists / therapeutic use

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Dopamine Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Serotonin
  • Serotonin Receptor Agonists