Serotonin Receptors as a Potential Therapeutic Target in Epilepsy

The development of antiepileptic drugs has focused particularly on neurotransmitters involved in excitatory and inhibitory regulation. Serotonin (5-HT), a regularly secreted neurotransmitter in the central nervous system, plays critical roles in the regulation of neural excitation. Accumulating evidence suggests that different 5-HT receptor subtypes may be useful in treating seizures. Recent data indicate that 7 different major subtypes of 5-HT receptors play different roles in the pathophysiology of epilepsy. A lot of studies have evaluated the effects of agonist or antagonist agents using one or more of these receptor subtypes on seizures in different animal seizure models. Evidence suggests that the role of serotonergic transmission in epilepsy is complex due to the diversity of 5-HT receptor subtypes. In general, activation of 5-HT1A/B, 5-HT2A/2C and 5-HT3 receptors inhibits seizures. Current studies on the role of 5-HT4 and 5-HT6 receptors in seizures are quite limited. Recent evidence shows that 5-HT7 receptor antagonists have an anticonvulsant effect. However, the exact role of each 5-HT receptor subtype on seizures remains unclear due to conflicting results in studies. Therefore, in this review, we aimed to reveal current data on the role of 5-HT receptors in epilepsy and to provide a detailed overview of the modulation of each 5-HT receptor in the pathophysiology or treatment of epilepsy.