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Association Between Sumatriptan Treatment During a Migraine Attack and Central 5-HT1B Receptor Binding

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Importance: Triptans, the most efficient acute treatment for migraine attacks, are 5-HT1B/1D receptor agonists, but their precise mechanism of action is not completely understood. The extent to which triptans enter the central nervous system and bind to 5-HT1B receptors in the brain is unknown.

Objectives: To determine the occupancy of sumatriptan to central 5-HT1B receptors, and to investigate changes in brain serotonin levels during migraine attacks.

Design, Setting, and Participants: This study of 8 patients in Denmark used a within-participant design and was conducted from April 20, 2015, to December 5, 2016. Participants were otherwise healthy patients with untreated episodic migraine without aura, aged between 18 and 65 years, and recruited from the general community. Data analysis was performed from January 2017 to April 2018.

Interventions: All participants underwent positron emission tomographic scans after injection of [11C]AZ10419369, a specific 5-HT1B receptor radiotracer. All participants were scanned 3 times: (1) during an experimentally induced migraine attack, (2) after a subcutaneous injection of 6-mg subcutaneous sumatriptan, and (3) on a migraine attack-free day. Scans 1 and 2 were conducted on the same study day. Each scan lasted for 90 minutes.

Main Outcome and Measure: The primary outcome was the nondisplaceable binding potential of [11C]AZ10419369 across 7 brain regions involved in pain modulation. The binding potential reflects receptor density, and changes in binding potential reflects displacement of the radiotracer. The occupancy of sumatriptan was estimated from the 2 scans before and after sumatriptan administration.

Results: Eight patients with migraine were included in the study; of these participants, 7 (87%) were women. The mean (SD) age of participants on study day 1 was 29.5 (9.2) years and on study day 2 was 30.0 (8.9) years. Sumatriptan was associated with statistically significantly reduced 5-HT1B receptor binding across pain-modulating regions (mean [SD] binding potential, 1.20 [0.20] vs 1.02 [0.22]; P = .001), corresponding to a mean (SD) drug occupancy rate of 16.0% (5.3%). Furthermore, during migraine attacks, as compared with outside of attacks, 5-HT1B receptor binding was statistically significantly associated with reduced in pain-modulating regions (mean [SD] binding potential, 1.36 [0.22] vs 1.20 [0.20]; P = .02).

Conclusions and Relevance: Treatment with sumatriptan during migraine attacks appeared to be associated with a decrease in 5-HT1B receptor binding, a finding that is most likely associated with the binding of sumatriptan to central 5-HT1B receptors, but the contribution of ongoing cerebral serotonin release to the lower binding cannot be excluded; the migraine attack-associated decrease in binding could indicate that migraine attacks are associated with increases in endogenous serotonin.

OriginalsprogEngelsk
TidsskriftJAMA Neurology
Vol/bind76
Udgave nummer7
Sider (fra-til)834-840
Antal sider7
ISSN2168-6149
DOI
StatusUdgivet - 1 jul. 2019

ID: 58077244