ADX-47273

ADX-47273 is a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5(EC50=170 nM).IC50 value: 170 nM(EC50) [1] [2]Target: positive allosteric modulator (PAM) of mGluR5in vitro: ADX-47273 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. 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 [2]. 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 [2]. ADX47273 had no effect on single-session and multi-session extinction, but administration of ADX47273 after a single retrieval trial enhanced subsequent fear extinction learning [3].

Research Areas >> Neurological Disease

[1]. de Paulis T, et al. Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes. J Med Chem. 2006 Jun 1;49(11):3332-44.

[2]. Liu F, et al. ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive activities. J Pharmacol Exp Ther. 2008 Dec;327(3):827-39.

[3]. Xu J, et al. Potentiating mGluR5 function with a positive allosteric modulator enhances adaptive learning. Learn Mem. 2013 Jul 18;20(8):438-45.

mavoglurant | L-Glutamine | CTEP (RO4956371) | LY 354740 | L-(+)Sodium glutamate | ADX-88178 | MPEP (Hydrochloride) | FITM | (S)-MCPG | Basimglurant | LY341495 | Dipraglurant | JNJ-40411813 | LY404039 | JNJ 16259685