Nelotanserin is a potent, selective 5-HT(2A) inverse agonist. Originally called ADP-125, the compound was developed by Arena Pharmaceuticals as a treatment for insomnia, but failed efficacy measures for this indication in Phase 2. In 2015, Axovant Sciences licensed this compound for development, renamed it nelotanserin, and began evaluating it in dementia with Lewy bodies (DLB). Both radioligand binding and functional inositol phosphate accumulation assays suggest that nelotanserin has low nanomolar potency on the 5-HT(2A) receptor with at least 30- and 5000-fold selectivity compared with 5-HT(2C) and 5-HT(2B) receptors, respectively. Nelotanserin dosed orally prevented (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 5-HT(2A) agonist)-induced hypolocomotion, increased sleep consolidation, and increased total nonrapid eye movement sleep time and deep sleep, the latter marked by increases in electroencephalogram (EEG) delta power. Nelotanserin has been used in trials studying the treatment of Lewy body dementia, visual hallucinations, dementia with Lewy bodies, and REM sleep behavior disorder.