JNJ-42153605 is a mGlu2 receptor positive allosteric modulator (EC50: 17 nM).

JNJ-42153605 has been evaluated for its specificity to the mGlu2 receptor, demonstrating no agonist or antagonist effects on other mGlu receptor subtypes at concentrations up to 30 μM. Additionally, it shows high permeability without evidence of P-glycoprotein efflux.

JNJ-42153605 demonstrates significant in vivo efficacy by suppressing REM sleep at a 3 mg/kg oral dose in rats, as observed in the sleep-wake EEG paradigm—a result attributed to mGlu2 mediation. Additionally, it mitigates PCP-induced hyperlocomotion in mice, indicating antipsychotic properties, with an effective dose (ED50) of 5.4 mg/kg subcutaneously. The compound is rapidly absorbed in the gastrointestinal tract, peaking at 0.5 hours post-administration. It exhibits moderate to high clearance rates in both rats and dogs (35 and 29 mL/min/kg, respectively), with relatively short elimination half-lives of 2.7 hours in rats and between 0.8 to 1.1 hours in dogs[1].