First GluN1/GluN3A-Selective Positive Allosteric Modulators Reported
- Two compounds, EU1180-437 and EU1180-490, potentiate glycine-gated GluN1/GluN3A receptors with low-micromolar potency and selectivity over GluN1/GluN3B and GluN2-containing NMDA receptors.
- Neither showed activity at a panel of other ionotropic and related receptors.
- In mouse hippocampal CA1 neurons they enhanced glycine-activated currents, an effect absent in GluN3A-knockout slices.
💡 Points Based on the abstract
The knockout-slice control is what makes these credible tools: it shows the slice effect is GluN3A-dependent rather than assay noise. They are still low-micromolar tool compounds, so brain exposure, metabolic stability and in vivo dosing are untested, which limits their use to ex vivo work. The useful next step is a behaviour or disease-model study with a matched inactive analogue to decide whether GluN3A potentiation is a target worth chasing.
📄 Paper · Molecular Pharmacology ↗ Selective Positive Allosteric Modulators of GluN1/GluN3A Receptors