Glutamate, the major excitatory neurotransmitter in the CNS, signals through both ionotropic and metabotropic glutamate receptors. Of the eight metabotropic glutamate receptors -mGlus) discovered thus far, development of inhibitors to mGlu5 has been given significant attention in preclinical models of disease, including pain, anxiety, gastresophageal reflux disease, Parkinson s associated dyskinesia, and fragile X syndrome, as well as in animal models of drug addiction. CAY10651 is a noncompetitive antagonist -negative allosteric modulator) of mGlu5 that demonstrates an IC50 value of 61 nM in a calcium mobilization assay and a Ki value of 477 nM in a radioligand binding assay. A 10 uM concentration of CAY10651 results in a near complete blockade of the glutamate response in cortical astrocytes. A 30 mg/kg dose of CAY10651 in mice yields potent inhibition in a marble burying model of anxiety and is efficacious in an operant sensation seeking model of addiction.
產(chǎn)品描述
A noncompetitive antagonist of mGlu5 -IC50 = 61 nM; Ki = 477 nM); 10 uM results in a near complete blockade of the glutamate response in cortical astrocytes; 30 mg/kg in mice yields potent inhibition in a marble burying model of anxiety and is efficacious in an operant sensation seeking model of addiction