5-HT2A inverse-agonists for the treatment of insomnia

Nearly one half of the adult population in the U. S. experience some symptoms of insomnia ( difficulties with getting to sleep, maintaining sleep, and/or sleep quality) on a weekly basis. Although most people with insomnia complain primarily of issues related to sleep maintenance and quality, current therapeutic approaches, including GABA(A) agonists, off label antidepressant use, H-1 antagonists and melatonin agonists, primarily address sleep onset latency. The overall sleep architecture, especially that of the deeper stages of NREM sleep known as slow wave sleep (SWS), plays a crucial role in restorative, restful sleep. Through the 5-HT2A receptor, serotonin plays an active role in the regulation of sleep architecture. Antagonists/inverse-agonists of 5-HT2A, such as APD125, volinanserin, eplivanserin, pruvanserin and pimavanserin, are currently being investigated as therapeutics that could improve the treatment of sleep maintenance and quality in people with insomnia.