Nelotanserin

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 5-HT2A 反向激动剂，pKi 为 9.2；与 5-HT2C 和 5-HT2B 受体相比，选择性高出 30 倍和 5000 倍。

A potent, selective 5-HT2A inverse agonist with pKi of 9.2; displays >30- and 5000-fold selectivity compared with 5-HT2C and 5-HT2B receptors; prevents DOI-induced hypolocomotion and increases sleep consolidation; orally active.Depression Phase 2 Discontinued(In Vitro):Results from IP accumulation assays suggest that 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. The results suggest that Nelotanserin has a 262-fold higher affinity for human 5-HT2A than 5-HT2C receptors and a 6610-fold higher affinity for human 5-HT2A than 5-HT2B receptors. (In Vivo):Each compound is tested in a minimum of five rats by oral gavage with administration occurring in the middle of the inactive period, 6 h after light onset. The delta power during non-REM sleep (NREMS) is significantly different between all the analogues tested and the vehicle control. Nelotanserin (Compound 39) produces significant increases in delta power that persist for the first 4 h following dosing. Significant differences are found, however, in NREMS bout length. Nelotanserin significantly increases NREMS bout length during the first hour following dosing, and 3 does so during the second hour. In conjunction with this increased NREM bout duration, the number of NREM bouts decrease during the first hour for Nelotanserin (p<0.01) as well as for compound 15 (p<0.05).

Results from IP accumulation assays suggest that 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. The results suggest that Nelotanserin has a 262-fold higher affinity for human 5-HT2A than 5-HT2C receptors and a 6610-fold higher affinity for human 5-HT2A than 5-HT2B receptors.

Each compound is tested in a minimum of five rats by oral gavage with administration occurring in the middle of the inactive period, 6 h after light onset. The delta power during non-REM sleep (NREMS) is significantly different between all the analogues tested and the vehicle control. Nelotanserin (Compound 39) produces significant increases in delta power that persist for the first 4 h following dosing. Significant differences are found, however, in NREMS bout length. Nelotanserin significantly increases NREMS bout length during the first hour following dosing, and 3 does so during the second hour. In conjunction with this increased NREM bout duration, the number of NREM bouts decrease during the first hour for Nelotanserin (p<0.01) as well as for compound 15 (p<0.05).

APD-125 | RVT-102

GPCR/G Protein

5-HT Receptor

5-HT Receptor

Neurological Disease

Depression

839713-36-9

437.2381

C18H15BrF2N4O2

>98% (HPLC)

DMSO: ≥ 32 mg/mL

O=C(NC1=CC=C(F)C=C1F)NC2=CC=C(OC)C(C3=C(Br)C=NN3C)=C2

Urea, N-[3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-N'-(2,4-difluorophenyl)-

(-20℃)

With Ice Pack

≥ 2 years