Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy?
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Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A
Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy?
Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17.
- PubMed ID
- 29352859 [ View in PubMed]
- Abstract
Migraine is a neurovascular disorder that involves activation of the trigeminovascular system and cranial vasodilation mediated by release of calcitonin gene-related peptide (CGRP). The gold standard for acute migraine treatment are the triptans, 5-HT1B/1D/(1F) receptor agonists. Their actions are thought to be mediated through activation of: (i) 5-HT1B receptors in cranial blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT1D receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5-HT1B/1D/1F receptors in central nervous system involved in (anti)nociceptive modulation. Unfortunately, coronary arteries also express 5-HT1B receptors whose activation would produce coronary vasoconstriction; hence, triptans are contraindicated in patients with cardiovascular disease. In addition, since migraineurs have an increased cardiovascular risk, it is important to develop antimigraine drugs devoid of vascular (side) effects. Ditans, here defined as selective 5-HT1F receptor agonists, were developed on the basis that most of the triptans activate trigeminal 5-HT1F receptors, which may explain part of the triptans' antimigraine action. Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials. Admittedly, the exact site of action is still unknown, but lasmiditan possess a high lipophilicity, which suggests a direct action on the central descending antinociceptive pathways. Furthermore, since 5-HT1F receptors are located on trigeminal fibers, they could modulate CGRP release. This review will be particularly focussed on the similarities and differences between the triptans and the ditans, their proposed sites of action, side effects and their cardiovascular risk profile.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Zolmitriptan 5-hydroxytryptamine receptor 1A Protein Humans NoAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1B Protein Humans YesAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1D Protein Humans YesAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1E Protein Humans UnknownAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1F Protein Humans YesAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 2A Protein Humans NoAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 2B Protein Humans NoAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 7 Protein Humans NoAgonistDetails