mGluR5 & migraine

Although the triggering events leading to migraine are poorly understood, migraine attacks are believed to be propagated by a positive feedback loop in the brain called the “migraine circuit.” In short, the migraine circuit includes stimulation of the brain cortex, dilation of meningeal blood vessels, inflammation and pain. The migraine circuit is known to involve several brain regions, including the cortex, the trigeminal nucleus caudalis, the trigeminal ganglion, the thalamus and the brain’s superficial blood vessels.

A chemical messenger, a “neurotransmitter”, known as serotonin has been shown to be important in accounting for some of the phenomena which occur during migraine. Triptans, the gold standard of migraine therapy, act on serotonin receptors in the brain to reverse dilation of brain blood vessels, thereby providing symptomatic relief. However, they do not appear to interrupt the migraine circuit or intervene in the underlying mechanism of migraine, hence they have not been developed as migraine preventative agents.

mGluR5 inhibition (ADX10059)
Recent research has shown that glutamate is the major neurotransmitter involved in the propagation of the migraine circuit. The metabotropic glutamate receptor 5 (mGluR5) is known to be expressed in key brain regions involved in the circuit. Thus, Addex postulated that ADX10059 could interrupt the migraine circuit to abort an active attack and potentially prevent an attack from being triggered.

ADX10059 in migraine
migraine