Description
ADX-47273 is a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5) with EC
50 values of 0.17 and 0.23 μM for potentiation of glutamate activity in HEK293 cells expressing rat mGluR5 and primary astrocyte cultures, respectively.
1 It is selective for mGluR5 over rat mGluR1 and human mGluR1 and mGluR4 when used at concentrations up to 10 μM.
In vivo, ADX-47273 (1 and 10 mg/kg, i.p.) increases ERK and CREB phosphorylation in the hippocampus and prefrontal cortex in rats. It decreases the conditioned avoidance response, apomorphine-induced climbing, as well as PCP-, apomorphine-, and amphetamine-induced locomotor activity in rats in a dose-dependent manner, indicating antipsychotic-like activity. ADX-47273 (0.1-50 mg/kg, i.p) improves recall in a novel object recognition test and reduces impulsivity in the 5-choice serial reaction time task (5CSRTT). It also enhances reversal learning in mice in the Morris water maze test.
2
Uses
ADX-47273 is a potent, selective and brain-penetrant mGluR5 positive allosteric modulator (PAM), with an EC50 of 0.17 μM for potentiation of glutamate (50 nM) response. ADX-47273 has antipsychotic and procognitive activities[1][2].
in vivo
adx47273 increased erk (extracellular signal-regulated kinase) and creb (camp-responsive element-binding protein) phosphorylation in rat hippocampus and prefrontal cortex. in rat and mouse models that sensitive to antipsychotic treatment, adx47273 decreased rat conditioned avoidance responding (minimal effective dose = 30 mg/kg i.p.) and reduced mouse ampomorphine-activated climbing (minimal effective dose = 100 mg/kg i.p.) [1]
References
[1] liu f, grauer s, kelley c, navarra r, graf r, zhang g, atkinson pj, popiolek m, wantuch c, khawaja x, smith d, olsen m, kouranova e, lai m, pruthi f, pulicicchio c, day m, gilbert a, pausch mh, brandon nj, beyer ce, comery ta, logue s, rosenzweig-lipson s, marquis kl. 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 precognitive activities. j pharmacol exp ther. 2008 dec;327(3):827-39.
