CPPHA, a positive allosteric modulator of glutamate receptors mGluR5 and mGluR1, is commonly used in development for central nervous system diseases.

CPPHA增强了亚阈浓度的3,5-二羟基苯甘氨酸（DHPG）对细胞外信号调节蛋白激酶（ERK）和cAMP响应元件结合蛋白（CREB）活性的影响，以及在皮层和海马切片中的N-甲基-D-天门冬氨酸（NMDA）受体亚单位NR1的磷酸化[1]。CPPHA将荧光Ca(2+)测定中对谷氨酸的阈反应增强了7至8倍（EC50s：400至800nM），并在10微摩尔浓度下将mGluR5激动剂对谷氨酸、鹿蕨酸和DHPG的浓度反应曲线向左移动了4至7倍。10微摩尔的CPPHA增强了海马切片中由DHPG诱导的NMDA受体电流，尽管它本身对这些电流没有影响。同样，10微摩尔的CPPHA也增强了大鼠下丘脑神经元DHPG诱发的mGluR5介导的去极化[2]。CPPHA提升了基础mGluR5介导的ERK1/2磷酸化水平，并增强了低浓度激动剂的效应。相比之下，CPPHA显著降低了高浓度激动剂诱导的ERK1/2磷酸化[3]。

CPPHA potentiated the response to a subthreshold concentration of 3,5-dihydroxy-phenylglycine (DHPG) on extracellular signal-regulated protein kinase (ERK) and cyclic-AMP responsive element-binding protein (CREB) activity, as well as N-methyl d-aspartate (NMDA) receptor subunit NR1 phosphorylation in cortical and hippocampal slices [1]. CPPHA potentiated threshold responses to glutamate in fluorometric Ca(2+) assays 7- to 8-fold (EC50s: 400 to 800 nM), and at 10 μM shifted mGluR5 agonist concentration-response curves to glutamate, quisqualate, and DHPG 4- to 7-fold to the left. CPPHA (10 μM) potentiated NMDA receptor currents in hippocampal slices induced by threshold levels of DHPG, whereas having no effect on these currents by itself. Similarly, 10 μM CPPHA also potentiated mGluR5-mediated DHPG-induced depolarization of rat subthalamic nucleus neurons [2]. CPPHA induced an increase in basal mGluR5-mediated ERK1/2 phosphorylation and potentiated the effect of low concentrations of agonists. In contrast, CPPHA significantly decreased ERK1/2 phosphorylation induced by high concentrations of agonists [3].