An mGluR4 and mGluR6 positive allosteric modulator and mGluR5 antagonist
VU0364770 is a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4; EC50 = 1.1 ?M in a calcium mobilization assay).1 It is also a positive allosteric modulator of mGluR6 (EC50 = 6.8 ?M) and an antagonist of mGluR5 (IC50 = 17.9 ?M). VU0364770 binds to monoamine oxidase A (MAO-A) and MAO-B (Kis = 8.5 and 7.2 ?M, respectively), as well as the human norepinephrine transporter in a panel of 68 receptors, ion channels, and transporters at 10 ?M. It decreases haloperidol-induced catalepsy and reduces increases in the number of premature reactions in response to a light cue, indicating improved attentional control, in a 6-hydroxydopamine rat model of Parkinson’s disease when administered at a dose of 56.6 mg/kg.
1.Jones, C.K., Bubser, M., Thompson, A.D., et al.The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with ?-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's diseaseJ. Pharmacol. Exp. Ther.340(2)404-421(2012)
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