Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT1F–G protein complex
- Resource Type
- Authors
- Yumu Zhang; H. Eric Xu; Yangxia Tan; Peiyu Xu; Sijie Huang; Yi Jiang; Chongzhao You
- Source
- Cell Research. 31:1036-1038
- Subject
- Drug
G protein
media_common.quotation_subject
Cell Biology
Biology
Pharmacology
medicine.disease
Lasmiditan
chemistry.chemical_compound
chemistry
Migraine
medicine
medicine.symptom
Ischemic heart
Inhibitory G-protein
Molecular Biology
Vasoconstriction
5-HT receptor
media_common
- Language
- ISSN
- 1748-7838
1001-0602
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.