Biological Activity
vu0361737 is a selective, positive allosteric modulator and brain-permeable for mglur4 (mglu4 receptor), (ec₅₀ = 240 and 110 nm for human and rat receptors respectively), >50 fold selectivity over other mglur subtypes. inactive at mglur-1, mglur-2, mglur-3, mglur-6 and mglur-7 receptors and showed weak activity at mglur-5 and mglur-8 receptors. [1]the mglur (metabotropic glutamate receptor) is a group of g-protein coupled receptors and is active through an indirect metabotropic process. mglur4 are invoinved in parkinson as it decrease gabaerigic transmission at inhibitory striato-pallidal synapse with the basal ganglia.[1][2]following the administration of vu0361737 into rat intraperitoneally (10mg/kg), the amount of compound present in brain and plasma was determined at 0.5, 1 and 8 hours. it showed a short half-life (t1/2 20 minutes) and a pronounced brain exposure (brain: plasma ratio = 4.1) [1]
References
[1] engers dw, niswender cm, weaver cd, jadhav s, menon un, zamorano r, conn pj, lindsley cw, hopkins cr. synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mglur4) positive allosteric modulators (pams). j med chem. 2009 jul 23;52(14):4115-8.
[2] engers dw, field jr, le u, zhou y, bolinger jd, zamorano r, blobaum al, jones ck, jadhav s, weaver cd, conn pj, lindsley cw, niswender cm, hopkins cr. discovery, synthesis, and structure-activity relationship development of a series of n-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mglu(4)) with cns exposure in rats. j med chem. 2011 feb 24;54(4):1106-10.
