Nelotanserin

SKU: orb1223893

Description

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.\n(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).

Key Properties

• CAS Number: 839713-36-9
• MW: 437.2381
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₅BrF₂N₄O₂
• SMILES: O=C(NC1=CC=C(F)C=C1F)NC2=CC=C(OC)C(C3=C(Br)C=NN3C)=C2
• Target: 5-HT Receptor
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• 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).
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

APD-125 | RVT-102

Quick Database Links

Gene Symbol

5-HT Receptor