With so many different neurotransmitters and pathways associated with migraine, several target-specific therapeutic agent classes are being developed. Drug classes with products now on the market or soon to be authorised include:6

·       Triptans – serotonin 5-HT1B/1D receptor agonists

·       Ditans – 5-HT1F receptor agonists,

·       Gepants – CGRP receptor antagonists;

·       CGRP mechanisms – monoclonal antibodies.

Triptans can inhibit the pain-sensing nociceptive inputs into the trigeminal and thalamus complex. So far, 14 serotonin/5-HT receptors have been identified. Most triptans act on 5-HT1B/1D receptors, but may also activate others. As serotonin 5-HT1B/1D receptor agonists, triptans may work on cranial vasculature but it seems a more likely site of action is on the 5-HT1D and 5-HT1F receptors in the TCC.

One drawback with triptans is their vasoconstriction activity which limits their use in people with cardiac risk factors. Being able to target the 5-HT1F receptor specifically could mean a triptan without vascular side effects, and this is the basis of a drug in development, lasmiditan, potentially the first in the drug class of ditans.

Less close to market authorisation are glurants, metabotropic glutamate receptor-5 (mGluR5) modulators. In migraine, they attenuate the spinal cord’s trigeminocervical complex (TCC) activity, interfering with trigeminal pain transmission. This receptor class is also being explored for novel antidepressants.6,22