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

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
• calcitonin gene-related peptide receptor antagonists
• dopamine receptor antagonists
• migraine attack therapy
• N-methyl-D-aspartate receptor inhibitors
• pituitary adenylate cyclase-activating polypeptide type 1 receptor

Notes

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