Lasmiditan migraine attack treatment

Aug 17, 2021

Lasmiditan, new treatment for migraine attacks

A new drug is currently being tested to treat migraine attacks; This is Lasmiditan , developed by Eli Lilly laboratories. It is an agonist of the 5-HT 1 F serotonin receptors . After successful phase 2 clinical trials, it was tested in phase 3 clinical trials (Kuca et al. 2018). In 2019, the first trials confirmed the effectiveness of the treatment in migraine attacks , with a significant reduction in pain within two hours of the onset of the attack (Lamb et al. 2019). The 5-HT 1 F receptor was first described in mice based on its sequence homology with the 5-HT 1 B and D receptors targeted by triptans. Interest focused on this receptor when the theory of purely vascular migraine took a back seat. If vasodilation of the cranial arteries is indeed present, it would be secondary to a dysfunction of the central nervous system . Peripheral vasoactive action on the arteries is therefore not necessary to treat the migraine attack. The 5-HT 1 F receptor is very little present in the periphery and almost absent at the vascular level, but it is found in abundance in the central nervous system , and in particular in the trigeminal nucleus (Vila-Pueyo et al. 2018).
To better understand you can read “ The basics: migraine mechanism
Several pharmaceutical laboratories have developed 5-HT 1 F receptor agonists, but only two have been tested in humans: Lasmiditan and the molecule LY334370, also developed by Eli Lilly. The latter, however, was unsuccessful due to very strong hepatotoxicity. Lasmiditan is therefore the only 5-HT 1 F receptor agonist likely to soon obtain marketing authorization . Its chemical structure differs greatly from triptans and a new class of drugs called " ditan " has been specially created. This particular structure allows Lasmiditan to have very good selectivity for the 5-HT 1 F receptor and to be able to pass the blood-brain barrier . This allows it to exert its effect centrally and potentially, directly in the nucleus of the trigeminal (caudal) nerve (Lamb et al. 2019). Furthermore, it is interesting to note that it does not exert any vasomotor action. 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