JNJ-18038683 is a 5-Hydroxytryptamine Type 7 (5-HT7) receptor antagonist with pKis of 8.19 and 8.20 for rat and human 5-HT7 in HEK293 cells, respectively.

5-HT7 receptor (human):8.2(pKi, in HEK293 cells ), 5-HT7 receptor (rat):8.19(pKi, in HEK293 cells )

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.

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.