Background:

Lasmiditan is a selective agonist of 5-HT1F receptor with Ki value of 2.21nM [1].

Lasmiditan shows great selectivity against 5-HT1F over other human recombinant 5-HT receptor subtypes as well as other members of 5-HT1 family. The Ki values for 5-HT2A-2C, 5-HT6 and 5-HT7 are all above 2μM. In the in vitro functional assay, lasmiditan shows high functional selectivity for 5-HT1F with EC50 value of 43.1nM. Moreover, oral administration of lasmiditan potently decreases the dural plasma protein extravasation with ID50 value of 2×104μg/kg in the migraine models. It also inhibits trigeminal stimulation-induced c-fos expression in the nucleus caudalis. Furthermore, lasmiditan is proved to be an effective treatment in acute migraine after the phase II trials. And the oral administration is found to be better than the intravenous administration [1, 2]

参考文献:
[1] Nelson D L, Phebus L A, Johnson K W, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia, 2010, 30(10): 1159-1169.
[2] Tfelt-Hansen P C, Olesen J. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials. The journal of headache and pain, 2012, 13(4): 271-275.