CP-465022 is a Noncompetitive AMPA Receptor Antagonist for Neurological Disease Research

The α-amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid receptor (AMPA receptor) is an ionic glutamate (iGluR) transmembrane receptor. Specifically, it can mediate the rapid synaptic transmission system in the central nervous system. AMPAR, together with other members of the ionic glutamate receptor (iGluR) family, N-methyl-D-aspartic acid receptors and kainic acid receptors (NMDARs and KARs), is a cationic permeable receptor tetramer. Besides, AMPA receptors are responsible for most of the rapid excitatory transmission in the central nervous system. So it enables them to effectively affect Aβ The relationship between level and synaptic activity. Moreover, AMPARs can also serve as independent activators of second messenger signals. At certain synapses, AMPAR can also directly mediate calcium influx, triggering various forms of postsynaptic plasticity.

Furthermore, AMPAR is an important participant of trigger cells, which is associated with a large number of nervous system diseases and brain injuries. Meanwhile, the number and subunit composition of AMPARs at the synapse determines the dynamics of rapid glutamate signaling. Nonetheless, the functional AMPAR on the cell surface is a tetramer. Therefore, the tetramer assembly of AMPAR represents a promising goal in regulating AMPAR-mediated signal transduction in health and disease. Now, we will introduce a selective noncompetitive AMPA receptor antagonist, CP-465022.

CP-465022 is a Noncompetitive AMPA Receptor Antagonist for Neurological Disease Research.

At first, CP-465022 is a potent, and selective noncompetitive AMPA receptor antagonist with anticonvulsant activity. CP-465022 is against Kainate-induced response with an IC50 of 25 nM in rat cortical neurons. CP-465022 provides a new tool to investigate the role of AMPA receptors in physiological and pathophysiological processes.

Secondly, CP-465022 1 µM for 10 min has little effect on peak NMDA-induced currents but reduces current measured at 8 s during NMDA application by 26%. Importantly, CP-465022 at 10 µM inhibits peak NMDA-induced currents in cortical neurons by 36%. Its currents were measured at 8 s by 70% d in primary cultures of cortical and cerebellar granule neurons. Particularly, CP-465022 1 µM for 10 min inhibits peak NMDA currents in cultured rat cerebellar granule neurons with mean inhibition of 19%. Obviously, NMDA currents measured at 8 s by 45%, similar to what is observed in the cortical neurons.
Thirdly, CP-465022 has inhibitory effects on Kainate-induced whole-cell currents in voltage-clamped rat hippocampal. Interestingly, 100 nM CP465,022 inhibits kainate currents developed over the course of 200s. 500 nM and 1 µM CP-465022 nearly completely inhibit this time frame (99.3%).

Finally, CP-465022 is a noncompetitive AMPA receptor antagonist for neurological disease research.


J T Lazzaro, et al. Neuropharmacology. 2002 Feb;42(2):143-53.