NMDA receptor subtype differential affinity as a key enabler for precision neuropsychiatry.
Progress in neuro-psychopharmacology & biological psychiatry June 20, 2026 Aline Freyssin, Reina Benabou, Hanna Zoe Müller et al.
A novel compound, RST-01, a fluoroalkyl derivative of amantadine, shows promise as a treatment for early PTSD in preclinical rat models, producing efficacy without the dissociative side effects or neurotoxic Olney's lesions associated with R,S-ketamine and memantine. In vitro electrophysiological assays measuring IC₅₀ values for human GluN1/GluN2A-D receptors revealed that RST-01 has a more differentiated selectivity profile across the four GluN2 subunits compared to ketamine or memantine. This distinct subunit-specific pharmacological signature offers a mechanistic explanation for the improved safety margins observed, supporting development of safer NMDAR-targeting therapies.