Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Electrical stimulation of the dura mater or the superior salivatory nucleus in anaesthetised rats evoked trigeminovascular or trigeminal-autonomic reflex activation at the level of the trigeminocervical complex. Additionally, cranial autonomic manifestations in response to trigeminal-autonomic 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-HT1F receptors in human post-mortem tissue and of several 5-HT1 receptor subtypes in specific tissue beds. KEY RESULTS:
Lasmiditan dose-dependently reduced trigeminovascular activation in a preclinical model of migraine. Lasmiditan also reduced superior salivatory nucleus-evoked activation of the trigeminal-autonomic reflex, but had no effect on cranial autonomic activation. mRNA profiling in human tissue showed expression of the 5-HT1F receptor in several structures relevant for migraine and cluster headache. CONCLUSION AND IMPLICATIONS: Our data suggest that lasmiditan acts, at least in part, as an anti- migraine 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. LINKED ARTICLES: 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 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.3/issuetoc.
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Authors | Marta Vila-Pueyo, Keith Page, Paul R Murdock, Howard J Loraine, Amanda J Woodrooffe, Kirk W Johnson, Peter J Goadsby, Philip R Holland |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 179
Issue 3
Pg. 358-370
(Feb 2022)
ISSN: 1476-5381 [Electronic] England |
PMID | 34600443
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The British Pharmacological Society. |
Chemical References |
- Benzamides
- Piperidines
- Pyridines
- RNA, Messenger
- Receptors, Serotonin
- serotonin 1F receptor
- Serotonin
- lasmiditan
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Topics |
- Animals
- Benzamides
- Cluster Headache
(drug therapy)
- Migraine Disorders
(drug therapy)
- Nociception
- Piperidines
- Pyridines
- RNA, Messenger
- Rats
- Receptors, Serotonin
- Serotonin
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