JNJ16259685

JNJ16259685的生物活性 JNJ16259685 is a selective antagonist at the mGlu1 receptors, and inhibits the synaptic activation of mGlu1 in a concentration-dependent manner with IC50 of 19 nM. IC50 value: 19 nM (mGlu1) Target: mGluR In vitro: NJ16259685 potently and completely inhibits the glutamate (30 μM)-induced increase in intracellular Ca2+ concentrations at the rat mGlu1a receptor with an IC50 value of 3.24±1.00 nM. IC50 values for CPCCOEt and BAY 36-7620 were 17.8±10.3 μM and 161±38 nM, respectively. The potency of JNJ16259685 in blocking glutamate (30 μM)-induced Ca2+ mobilization at the human mGlu1a receptor was 1.21±0.53 nM (IC50 value, n=3). As shown in Fig. 2, JNJ16259685 inhibited the glutamate (3 μM)-induced rise in intracellular Ca2+ concentrations at the rat mGlu5a receptor with an IC50 value of 1.31±0.39 μM (n=4). JNJ16259685 blocked glutamate (3 μM)-induced Ca2+?mobilization at the human mGlu5 receptor with an IC50 of 28.3±11.7 μM (n=4, Fig. 2). JNJ16259685 did not exhibit agonist activity at any of the group I mGlu receptors[3]. In vivo: JNJ16259685; 0.125, 0.25, 0.5, 1, 2, 4 and 8?mg/kg, i.p) significantly reduces the time spent in digging behaviours (0.25-8 mg/kg), threat (all doses) and attack , in comparison with vehicle group[1]. JNJ16259685 (30 mg/kg) produces very minimal effects on locomotor activity. JNJ16259685 dramatically reduces rearing behavior, exploration of a novel environment and lever pressing for a food reward (rat: 0.3 mg/kg; mouse: 1 mg/kg). Subcutaneously administered JNJ16259685 (30 mg/kg) has no effect on reflexive startle responses to loud auditory stimuli or foot shock in mice[2]. JNJ16259685 exhibits high potencies in occupying central mGlu1 receptors in the rat cerebellum and thalamus ( = 0.040 and 0.014 mg/kg, respectively)[3]. JNJ16259685 is diluted in saline (90%) plus DMSO (10%).