| References: |
ADX-47273 is a novel, potent and selective metabotropic glutamate receptor 5 allosteric modulator with an EC50 of 170 nM. ADX-47273 shifted mGlu5 receptor glutamate response curve to the left. ADX-47273 elevated extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex.ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone], a recently identified potent and selective mGlu5 PAM, increased (9-fold) the response to threshold concentration of glutamate (50 nM) in fluorometric Ca(2+) assays (EC(50) = 170 nM) in human embryonic kidney 293 cells expressing rat mGlu5. In the same system, ADX47273 dose-dependently shifted mGlu5 receptor glutamate response curve to the left (9-fold at 1 microM) and competed for binding of [(3)H]2-methyl-6-(phenylethynyl)pyridine (K(i) = 4.3 microM), but not [(3)H]quisqualate. In vivo, ADX47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. In models sensitive to antipsychotic drug treatment, ADX47273 reduced rat-conditioned avoidance responding [minimal effective dose (MED) = 30 mg/kg i.p.] and decreased mouse apomorphine-induced climbing (MED = 100 mg/kg i.p.), with little effect on stereotypy or catalepsy. Furthermore, ADX47273 blocked phencyclidine, apomorphine, and amphetamine-induced locomotor activities (MED = 100 mg/kg i.p.) in mice and decreased extracellular levels of dopamine in the nucleus accumbens, but not in the striatum, in rats. In cognition models, ADX47273 increased novel object recognition (MED = 1 mg/kg i.p.) and reduced impulsivity in the five-choice serial reaction time test (MED = 10 mg/kg i.p.) in rats. Taken together, these effects are consistent with the hypothesis that allosteric potentiation of mGlu5 may provide a novel approach for development of antipsychotic and procognitive agents. For the detailed information of ADX 47273, the solubility of ADX 47273 in water, the solubility of ADX 47273 in DMSO, the solubility of ADX 47273 in PBS buffer, the animal experiment (test) of ADX 47273, the cell expriment (test) of ADX 47273, the in vivo, in vitro and clinical trial test of ADX 47273, the EC50, IC50,and affinity,of ADX 47273, For the detailed information of ADX 47273, the solubility of ADX 47273 in water, the solubility of ADX 47273 in DMSO, the solubility of ADX 47273 in PBS buffer, the animal experiment (test) of ADX 47273, the cell expriment (test) of ADX 47273, the in vivo, in vitro and clinical trial test of ADX 47273, the EC50, IC50,and affinity,of ADX 47273, Please contact DC Chemicals. |
