Radiprodil's block of NMDA receptors in dopamine neurons turns out to be partial and fades at high doses
- Radiprodil, a GluN2B-selective NMDA receptor modulator being tested as a paediatric antiepileptic, was examined in dopamine neurons of young rat midbrain slices using patch-clamp recordings.
- Inhibition was only partial and, unexpectedly, weakened as concentrations rose, while single-channel current also dipped slightly.
- A kinetic model with a second, inhibition-opposing radiprodil site fit the data, a caution for allosteric modulator design.
💡 Points Based on the abstract
A bell-shaped response is a red flag for exposure-response work: in a seizure model, a higher dose could underperform a mid one. Neonatal rat nigral neurons are also a narrow proxy. The same curves on cortical or hippocampal GluN2B-containing receptors would help, as would a mutagenesis test of the proposed second site.