JNJ-18038683

SKU: orb1309526

Description

JNJ-18038683 is a potent and selective 5-HT7 receptor antagonist, exhibiting high affinity for both human and rat receptors. This compound is a valuable research tool for investigating the role of the 5-HT7 receptor in neuropsychiatric disorders, utilizing in vitro binding assays and in vivo behavioral models.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 851376-05-1
• MW: 529.97
• Purity: 98.31%
• Formula: C₂₆H₂₈ClN₃O₇
• SMILES: OC(=O)CC(O)(CC(O)=O)C(O)=O.Clc1ccc(cc1)-c1nn(Cc2ccccc2)c2CCNCCc12
• Target: 5-HT Receptor
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (9.43 mM);DMSO:200 mg/mL (377.38 mM)

Bioactivity

• Target IC50:
  5-HT7 receptor (rat):8.19(pKi, in HEK293 cells )|5-HT7 receptor (human):8.2(pKi, in HEK293 cells )
• In Vivo:
  JNJ-18038683 dose-dependently reduces REM sleep, particularly within the first 4 hours post-administration, with a significant decrease observed from a dosage of 1 mg/kg (P<0.05). Furthermore, it extends REM sleep latency, showing a significant prolongation at the highest dose tested (10 mg/kg; P<0.05), indicating that these effects are specific to the REM sleep state. An additional study evaluated the impact of administering JNJ-18038683 daily for 7 days (1 mg/kg s.c. per day) on EEG sleep patterns in rats, focusing on REM sleep both during treatment and after its cessation. Initial treatment significantly reduced REM sleep duration in the first 8 hours and increased REM latency, which remained elevated throughout the 7-day treatment but returned to normal after treatment stopped. While the reduction in REM sleep persisted during the treatment period, a rebound increase in REM sleep occurred upon treatment discontinuation. Neither the latency nor the total time of NREM sleep was impacted over the treatment course.
• In Vitro:
  JNJ-18038683 produces a concentration-dependent decrease of 5-HT (100 nM)-stimulated adenylyl cyclase. The pKB values determined for JNJ-18038683 are in good agreement with the corresponding Ki values determined from [3H]5-CT binding studies.JNJ-18038683 displaced, with high affinity, specific [3H]5-CT binding sites from rat and human 5-HT7 receptor express in HEK293 cells (pKi=8.19±0.02 and 8.20±0.01, respectively). Similar values are obtained on the native 5-HT7 in membranes from rat thalamus (pKi=8.50±0.20). Hill slope values are close to unity, suggesting one-site competitive binding. Antagonist potency of JNJ-18038683 is determined by the measurement of adenylate cyclase activity in HEK293 cells expressing the human or rat 5-HT7 receptor. 5-HT stimulates adenylyl cyclase activity in rat and human 5-HT7/HEK293 cells with a pEC50 of 8.09 and 8.12, respectively.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

5-HT Receptor, 5HT Receptor, 5HTReceptor, 5-hydroxytryptamine Receptor, Human 5-HT7 Receptor, JNJ18038683, JNJ-18038683, JNJ 18038683, Inhibitor, inhibit, Serotonin Receptor, Rat 5-HT7 Receptor

Compound Identifiers

PubChem CID

11249539