VU0364770 (VU 0364770)(EC50=1.1 μM), a positive allosteric modulator(PAM) of mGlu4, shows insignificant activity at 68 other receptors, including other mGlu subtypes.

mGlu4:1.1 μM(EC50)

VU0364770是一种有效的mGlu4正向异构调节剂，显示出在EC20浓度的谷氨酸存在下，对人mGlu4的潜力为1.1 ± 0.2 μM，并将谷氨酸浓度-反应曲线向左移动31.4 ± 4.0倍。在大鼠mGlu4上，VU0364770展示出290 ± 80 nM的活性，并促使谷氨酸浓度-反应曲线左移18.1 ± 1.7倍。[1]

VU0364770单独使用或与l-DOPA或正在临床开发中的腺苷2A（A2A）受体拮抗剂preladenant合用时显示出疗效。单独使用时，VU0364770能有效逆转由haloperidol引起的僵直、由单侧6-羟基多巴胺（6-OHDA）损伤造成的前肢不对称性以及由双侧6-OHDA损害黑质-纹状体引起的注意力缺陷。此外，与preladenant联合使用时，能增强逆转haloperidol引起的僵直症状。当VU0364770与无活性剂量的l-DOPA联合给药时，可以增强逆转前肢不对称性的效果，这表明mGlu4正向异构调节剂可能具有节省l-DOPA用量的活性。[1]

The effects of VU0364770 on rat mGlu1 and mGlu5 are assessed by using calcium mobilization and measuring the glutamate concentration-response relationship in the presence and absence of 10 μM VU0364770. Using a double-addition protocol, VU0364770 is added to the cells, followed 2.5 min later by a full concentration-response of glutamate. Shifts of the concentration-response relationship are used to assess potential potentiator (left shift of more than 2-fold) or antagonist (right shift of more than 2-fold or depression of the maximum response by at least 75%) activity of VU0364770. Compounds are further assessed for mGlu5 antagonist activity by performing a full concentration-response curve, starting at 30 μM and serially diluted it by using 1:3 dilutions, in the presence of an EC80 concentration of glutamate[1].