Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Deen M

PROVIDER: S-EPMC6547094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy.This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P??=??.87). The proportions of subjects experiencing pain relief (P?????.48); reductions in migraine pain intensity (P?????.78); and relief from nausea, photophobia, or phonophobia (P?????.88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M??=??2.6 vs M??=??2.4, P??=??.81) and the mean number of rescue medications used (M??=??.11 vs M??=??.26, P??=??.32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n??=??14 [44%]; 6 mg, n??=??18 [56%], P??=??.60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events.The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.