Metabotropic glutamate receptors (mGlu) are a family of class C G-protein-coupled receptors responsible for the fine-tuning of synaptic efficacy. The mGlu2 receptor is a member of the group II subfamily that negatively regulates the release of glutamate and GABA. JNJ-42153605 is a potent and selective mGlu2 positive allosteric modulator with an EC50 value of 17nM and Emax of 285%. The IC50 value of JNJ-42153605 for mGlu2 PAM binding is 15nM. The lipophilic ligand efficiency and lipophilicity-corrected ligand efficiency values of JNJ-42153605 are 5.2 and 9.8, respectively. The oral administration of JNJ-42153605 (3mg/kg) suppressed rapid eye movement (REM) sleep in mice during the first 2 h after treatment when compared to vehicle controls. JNJ-42153605 also prolonged the onset latency of REM sleep onset in mice. In the mouse model of phencyclidine-induced hyperlocomotion, JNJ-42153605 significantly attenuated phencyclidine-induced locomotor activity in a dose-dependent manner with an ED50 of 5.4mg/kg[4]. In the 6 Hz (32 mA stimulus intensity) model, median effective dose (ED50) values for JNJ‐42153605 were 3.8 mg/kg[5].
搜索
