Serotonin Receptors for Treatment of Insomnia

Abstract

Insomnia is characterized by complaints about sleep such as difficulty in falling asleep, abnormality in sleep architecture, and reduction in total sleep time, resulting in serious impairments in daytime activities. It has been suggested that insomnia usually has comorbity with medical and psychiatric disorders including anxiety, depression, and substance misuse disorders, which could be a risk factor for new onset psychiatric disorders. Though there are a number of drugs targeting various receptors such as zolpidem (a benzodiazepine receptor agonist), zaleplon (a anonbenzodiazepine modulator of GABA-A receptor), and ramelteon (a melatonin receptor agonist), these medications do not completely cure insomnia and have a variety of side effects. Currently, trazodone, a 5-HT2A receptor antagonist, was widely prescribed as sleep aids in the United States without FDA indication for insomnia and recent studies have also shown that lumateperone as 5-HT2A receptor antagonist improve the quality of sleep. Additionally, it has been proposed that 5-HT7 receptor is involved in regulation of sleep-wake cycle. 5-HT7 receptor modulators, such as SB-269970, LP-44, JNJ-18038683, and a β-arrestin biased ligand altered sleep parameters. Therefore, serotonin receptors could be powerful targets for treatment of insomnia.