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Serotonin receptors in epilepsy: Novel treatment targets?

ABSTRACT: Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5-HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each "5-HT subtype" separately and its relation to "epilepsy or seizures." Most research underlines the antiseizure activity of 5-HT_{1A,1D,2A,2C,3} agonism and 5-HT₆ antagonism. Consistently, FA, which has recently been approved for the treatment of seizures in Dravet syndrome, is an agonist of 5-HT_1D,2A,2C receptors. Even though each study focused on a distinct seizure/epilepsy type and generalization of different findings could lead to false interpretations, we believe that the available preclinical and clinical studies emphasize the role of serotonergic modulation, especially stimulation, as a promising avenue in epilepsy treatment.

SUBMITTER: Sourbron J

PROVIDER: S-EPMC9159250 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Serotonin receptors in epilepsy: Novel treatment targets?

Sourbron Jo J Lagae Lieven L

Epilepsia open 20220202 2

Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one o ...[more]

PMID: 35075810

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Serotonin receptors in epilepsy: Novel treatment targets?

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Serotonin receptors in epilepsy: Novel treatment targets?

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