The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse
Abstract Background The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting antimigraine drugs are currently being developed, among which the small molecu...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s10194-019-1007-y |
| _version_ | 1818974960993959936 |
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| author | Willem Sebastiaan van Hoogstraten Antoinette MaassenVanDenBrink |
| author_facet | Willem Sebastiaan van Hoogstraten Antoinette MaassenVanDenBrink |
| author_sort | Willem Sebastiaan van Hoogstraten |
| collection | DOAJ |
| description | Abstract Background The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting antimigraine drugs are currently being developed, among which the small molecule CGRP receptor antagonists, gepants, and the 5-HT1F receptor agonist lasmiditan. Whether treatment with these drugs carries the same risk for developing MOH is currently unknown. Main body Pathophysiological studies on MOH in animal models have suggested that decreased 5-hydroxytryptamine (5-HT, serotonin) levels, increased calcitonin-gene related peptide (CGRP) expression and changes in 5-HT receptor expression (lower 5-HT1B/D and higher 5-HT2A expression) may be involved in MOH. The decreased 5-HT may increase cortical spreading depression frequency and induce central sensitization in the cerebral cortex and caudal nucleus of the trigeminal tract. Additionally, low concentrations of 5-HT, a feature often observed in MOH patients, could increase CGRP expression. This provides a possible link between the pathways of 5-HT and CGRP, targets of lasmiditan and gepants, respectively. Since lasmiditan is a 5-HT1F receptor agonist and gepants are CGRP receptor antagonists, they could have different risks for developing MOH because of the different (over) compensation mechanisms following prolonged agonist versus antagonist treatment. Conclusion The acute treatment of migraine will certainly improve with the advent of two novel classes of drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT1F receptor agonism in relation to MOH, as well as the effects of chronic CGRP receptor blockade, are awaited with interest. |
| first_indexed | 2024-12-20T15:48:22Z |
| format | Article |
| id | doaj.art-ace60e91d26f4d44a26625e385eedfc0 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-20T15:48:22Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-ace60e91d26f4d44a26625e385eedfc02022-12-21T19:34:48ZengBMCThe Journal of Headache and Pain1129-23691129-23772019-05-012011710.1186/s10194-019-1007-yThe need for new acutely acting antimigraine drugs: moving safely outside acute medication overuseWillem Sebastiaan van Hoogstraten0Antoinette MaassenVanDenBrink1Dept. of Neuroscience Erasmus University Medical CentreDiv. of Pharmacology, Dept. of Internal Medicine, Erasmus University Medical CentreAbstract Background The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting antimigraine drugs are currently being developed, among which the small molecule CGRP receptor antagonists, gepants, and the 5-HT1F receptor agonist lasmiditan. Whether treatment with these drugs carries the same risk for developing MOH is currently unknown. Main body Pathophysiological studies on MOH in animal models have suggested that decreased 5-hydroxytryptamine (5-HT, serotonin) levels, increased calcitonin-gene related peptide (CGRP) expression and changes in 5-HT receptor expression (lower 5-HT1B/D and higher 5-HT2A expression) may be involved in MOH. The decreased 5-HT may increase cortical spreading depression frequency and induce central sensitization in the cerebral cortex and caudal nucleus of the trigeminal tract. Additionally, low concentrations of 5-HT, a feature often observed in MOH patients, could increase CGRP expression. This provides a possible link between the pathways of 5-HT and CGRP, targets of lasmiditan and gepants, respectively. Since lasmiditan is a 5-HT1F receptor agonist and gepants are CGRP receptor antagonists, they could have different risks for developing MOH because of the different (over) compensation mechanisms following prolonged agonist versus antagonist treatment. Conclusion The acute treatment of migraine will certainly improve with the advent of two novel classes of drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT1F receptor agonism in relation to MOH, as well as the effects of chronic CGRP receptor blockade, are awaited with interest.http://link.springer.com/article/10.1186/s10194-019-1007-yMigraineMedication overuse headacheChronic migraineAcute antimigraine drugsTriptansGepants |
| spellingShingle | Willem Sebastiaan van Hoogstraten Antoinette MaassenVanDenBrink The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse The Journal of Headache and Pain Migraine Medication overuse headache Chronic migraine Acute antimigraine drugs Triptans Gepants |
| title | The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse |
| title_full | The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse |
| title_fullStr | The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse |
| title_full_unstemmed | The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse |
| title_short | The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse |
| title_sort | need for new acutely acting antimigraine drugs moving safely outside acute medication overuse |
| topic | Migraine Medication overuse headache Chronic migraine Acute antimigraine drugs Triptans Gepants |
| url | http://link.springer.com/article/10.1186/s10194-019-1007-y |
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