生物活性

• 描述Nelotanserin is a potent 5-HT2A full inverse agonist (IC50 = 1.7 nM), a moderately potent 5-HT2C partial inverse agonist (IC50 = 79 nM) (maximal response was 62% of the response obtained for the reference inverse agonist clozapine), and a weak 5-HT2B inverse agonist (IC50 = 791 nM). Nelotanserin displays high affinity for recombinant human 5-HT2A receptors (Ki = 0.35 nM), moderate affinity for human 5-HT2C receptors (Ki = 100 nM), and low affinity for human 5-HT2B receptors (2000 nM) stably expressed in HEK293 cells. 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^[1]. Nelotanserin, both consolidate the stages of NREM sleep, resulting in fewer awakenings, and increase a physiological measure of sleep intensity^[2].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02640729	Lewy Body Dementia ... more >> Visual Hallucinations Collapse <<	Phase 2	Completed	-	United States, California ... more >> US123 Fountain Valley, California, United States, 92708 United States, Florida US114 Boca Raton, Florida, United States, 33486 US113 Orlando, Florida, United States, 32806 United States, Kansas US132 Lenexa, Kansas, United States, 66214 United States, Minnesota US103 Rochester, Minnesota, United States, 55905 United States, Nebraska US129 Lincoln, Nebraska, United States, 68526 United States, North Carolina US101 Chapel Hill, North Carolina, United States, 27514 United States, Ohio US104 Cleveland, Ohio, United States, 44195 US105 Columbus, Ohio, United States, 43210 United States, Texas US131 San Antonio, Texas, United States, 78229 Collapse <<
  NCT02871427	Lewy Body Dementia ... more >> Dementia With Lewy Bodies Parkinson's Disease Dementia Visual Hallucinations REM Sleep Behavior Disorder Collapse <<	Phase 2	Active, not recruiting	July 2019	United States, Alabama ... more >> US120 Birmingham, Alabama, United States, 35294 United States, Arkansas US143 Little Rock, Arkansas, United States, 77205 United States, Florida US114 Boca Raton, Florida, United States, 33486 US180 Maitland, Florida, United States, 32751 US154 Ocala, Florida, United States, 34471 US113 Orlando, Florida, United States, 32806 US152 Ormond Beach, Florida, United States, 32174 United States, Indiana US107 Indianapolis, Indiana, United States, 46202 United States, Kansas US132 Lenexa, Kansas, United States, 66214 United States, Minnesota US103 Rochester, Minnesota, United States, 55905 United States, Nebraska US129 Lincoln, Nebraska, United States, 68526 United States, North Carolina US101 Chapel Hill, North Carolina, United States, 27514 United States, North Dakota US147 Fargo, North Dakota, United States, 58103 United States, Ohio US111 Cincinnati, Ohio, United States, 45229 US104 Cleveland, Ohio, United States, 44195 US105 Columbus, Ohio, United States, 43210 United States, Rhode Island US173 Lincoln, Rhode Island, United States, 02865 United States, Tennessee US128 Memphis, Tennessee, United States, 38163 United States, Texas US131 San Antonio, Texas, United States, 78229 Collapse <<
  NCT02708186	Dementia With Lewy Bodies ... more >> REM Sleep Behavior Disorder Parkinson's Disease Dementia Collapse <<	Phase 2	Completed	-	-

• 参考文献

• [1] Al-Shamma HA, Anderson C, Chuang E, et al. Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia. J Pharmacol Exp Ther. 2010;332(1):281-290

  [2] Teegarden BR, Li H, Jayakumar H, et al. Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia. J Med Chem. 2010;53(5):1923-1936