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bioRxiv · 10.1101/2021.05.29.446083

Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT1F-G protein complex

Huang, S.·Xu, p.·Tan, Y.·You, C.·Zhang, Y.·Jiang, Y.·Xu, H. E.
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Abstract

Migraine headache has become global pandemics and is the number one reason of work day loss. The most common drugs for anti-migraine are the triptan class of drugs that are agonists for serotonin receptors 5-HT1B and 5-HT1D. However, these drugs have side effects related to vasoconstriction that could have fatal consequences of ischemic heart disease and myocardial infarction. Lasmiditan is a new generation of anti-migraine drug that selectively binds to the serotonin receptor 5-HT1F due to its advantage over the tripan class of anti-migraine drugs. Here we report the cryo-EM structure of the 5-HT1F in complex with Lasmiditan and the inhibitory G protein heterotrimer. The structure reveals the mechanism of 5-HT1F-selective activation by Lasmiditan and provides a template for rational design of anti-migraine drugs.

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Huang, S., Xu, p., Tan, Y., You, C., Zhang, Y., Jiang, Y., Xu, H. E.. 2021-05-29. Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT1F-G protein complex. https://doi.org/10.1101/2021.05.29.446083

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