{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:06:11Z","timestamp":1780329971587,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Lasmiditan is a novel selective 5\u2010HT<jats:sub>1F<\/jats:sub> receptor agonist, recently approved for acute treatment of migraine. 5\u2010HT<jats:sub>1F<\/jats:sub> receptors are widely expressed in the CNS and trigeminovascular system. Here, we have explored the therapeutic effects of 5\u2010HT<jats:sub>1F<\/jats:sub> receptor activation in preclinical models of migraine and cluster headache.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Electrical stimulation of the dura mater or the superior salivatory nucleus in anaesthetised rats evoked trigeminovascular or trigeminal\u2013autonomic reflex activation at the level of the trigeminocervical complex. Additionally, cranial autonomic manifestations in response to trigeminal\u2013autonomic reflex activation were measured, via anterior choroidal blood flow alterations. These responses were then challenged with lasmiditan. We explored the tissue distribution of mRNA for 5\u2010HT<jats:sub>1F<\/jats:sub> receptors in human post\u2010mortem tissue and of several 5\u2010HT<jats:sub>1<\/jats:sub> receptor subtypes in specific tissue beds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Lasmiditan dose\u2010dependently reduced trigeminovascular activation in a preclinical model of migraine. Lasmiditan also reduced superior salivatory nucleus\u2010evoked activation of the trigeminal\u2013autonomic reflex, but had no effect on cranial autonomic activation. mRNA profiling in human tissue showed expression of the 5\u2010HT<jats:sub>1F<\/jats:sub> receptor in several structures relevant for migraine and cluster headache.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our data suggest that lasmiditan acts, at least in part, as an anti\u2010migraine agent by reducing trigeminovascular activation. Furthermore, our results highlight a clear action for lasmiditan in a preclinical model of cluster headache. Given the proven translational efficacy of this model, our data support the potential utility of lasmiditan as a therapeutic option for the acute treatment of cluster headache attacks.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Advances in Migraine and Headache Therapy (BJP 75th Anniversary). To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.3\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.3\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15699","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T11:54:20Z","timestamp":1633348460000},"page":"358-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The selective 5\u2010HT<sub>1F<\/sub> receptor agonist lasmiditan inhibits trigeminal nociceptive processing: Implications for migraine and cluster headache"],"prefix":"10.1111","volume":"179","author":[{"given":"Marta","family":"Vila\u2010Pueyo","sequence":"first","affiliation":[{"name":"Headache Group, Wolfson Centre for Age\u2010Related Diseases, Institute of Psychiatry, Psychology &amp; 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