JNJ-18038683 (C09-1140-902)

JNJ-18038683 is a 5-Hydroxytryptamine Type 7 ( 5-HT 7 ) receptor antagonist, with pK i s of 8.19, 8.20 for rat and human 5-HT 7 in HEK293 cells, respectively.In VitroJNJ-18038683 displaced, with high affinity, specific [ 3 H]5-CT binding sites from rat and human 5-HT 7 receptor express in HEK293 cells (pK i =8.19±0.02 and 8.20±0.01, respectively). Similar values are obtained on the native 5-HT 7 in membranes from rat thalamus (pK i =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-HT 7 receptor. 5-HT stimulates adenylyl cyclase activity in rat and human 5-HT 7 /HEK293 cells with a pEC 50 of 8.09 and 8.12, respectively. JNJ-18038683 produces a concentration-dependent decrease of 5-HT (100 nM)-stimulated adenylyl cyclase. The pK B values determined for JNJ-18038683 are in good agreement with the corresponding K i values determined from [ 3 H]5-CT binding studies. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoJNJ-18038683 dose-dependently suppresses REM sleep mainly during the first 4 h after the treatment. The duration of REM sleep is significantly decreased from the dose of 1 mg/kg onward (P<0.05) during the first 4 h after oral administration. Concomitantly, the REM sleep latency tends to be prolonged in a dose-related manner with a significant increase in REM latency occurring only at the highest dose tested (10 mg/kg; P<0.05). These alterations in REM sleep seem to be state-specific. A separate study is conducted to determine whether repeated administration of JNJ-18038683 for 7 days would result in an adaptation of the EEG sleep response in particular on REM sleep in rats during the course of the treatment and after its discontinuation. JNJ-18038683 is administered for 7 consecutive days (1 mg/kg s.c. per day) at 2 h into the light phase. On the first day of treatment, JNJ-18038683 produces a significant decrease in the time spent in REM sleep during the first 8 h after the injection and a prolongation of the REM sleep latency. The REM sleep latency is increased during the 7-day repeated treatment and is normalized on the first recovery day after cessation of treatment. The significant decrease in REM sleep time is maintained during the 7-day repeated treatment, with a rebound occurring on the first recovery day after treatment discontinuation. The NREM sleep latency and the total NREM sleep time are not affected during the entire treatment . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:Rat 5-HT 7 Receptor 8.19 (pKi, in HEK293 cells ) Human 5-HT 7 Receptor 8.20 (pKi, in HEK293 cells ). Specification: 0.99 Molecular Formula: C26H28ClN3O7 Molecular Weight: 529.97 PubChem CID: 11249539 Isomeric SMILES: C1CNCCC2=C1C(=NN2CC3=CC=CC=C3)C4=CC=C(C=C4)Cl.C(C(=O)O)C(CC(=O)O)(C(=O)O)O