Biological Activity
GNE-8324 is a potent and selective NMDA receptor PAM.
In Vitro
Both GNE-6901 and GNE-8324 increase Glu potency, whereas neither PAM had significant effects on glycine (Gly) potency. Furthermore, both compounds slowed channel deactivation kinetics. However, GNE-8324 caused significantly slower NMDAR current deactivation following the termination of Glu application, compared to GNE-6901. Interestingly, when Gly was removed following the rapid Glu/Gly application in the constant presence of Glu, NMDAR currents rapidly deactivated in the presence of either GNE-6901 or GNE-8324, which is in sharp contrast to the slower NMDAR current deactivation in the presence of GNE-8324 when Gly was not removed. The authors argued that this demonstrated a specific interaction of PAMs with Glu but not Gly. However, these data also suggest that the slower NMDAR current deactivation in the presence of GNE-8324, but not GNE-6901, is highly dependent on ambient Gly concentration. GNE-8324 also markedly increased potency of Glu at GluN1/GluN2A NMDARs by about 10-fold while GNE-6901 had a much smaller effect on Glu potency. Finally GNE-8324 potency was strongly dependent on Glu concentration, whereas Glu concentration had only a modest effect on GNE-6901 potency. The deferential effects of GNE-6901 and GNE-8324 on GluN1/GluN2A NMDAR function could reflect subtle differences in modes of action of these closely related compounds, which might lead to distinct actions on NMDAR modulation in physiological settings.
In Vivo
No in vivo data are provided in the current product source. Contact us for further information.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.