Glutamatergic fine tuning with ADX-10059: a novel therapeutic approach for migraine?
BACKGROUND
Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives.


METHODS
The triptans, serotonin 5-HT(1B/1D) receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention.


RESULTS
The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches.


CONCLUSIONS
Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated.
Marin
Juana C A
JC
The National Hospital for Neurology and Neurosurgery, Institute of Neurology, Headache Group, Queen Square, London, UK.
Goadsby
Peter J
PJ
D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018683:Excitatory Amino Acid Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D015507:Drugs, Investigational; D018683:Excitatory Amino Acid Agents; C578935:GRM5 protein, human; D005765:Gastrointestinal Agents; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate