(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders.
International journal of molecular sciences June 20, 2024 Hana Shafique, Julie C Demers, Julia Biesiada et al. 29 citations
NMDA receptor antagonists show promise for neurological and psychiatric conditions such as neurodegenerative diseases, epilepsy, traumatic brain injury, substance use disorder, and major depressive disorder. (S)-ketamine was the first rapid-acting antidepressant approved for medical use. Its stereoisomer, (R)-ketamine (arketamine), is under development for treatment-resistant depression and has shown efficacy in multiple animal models. Two clinical studies reported efficacy in treatment-resistant depression and bipolar depression, though a sponsor study failed to meet primary endpoints; post hoc analysis indicated efficacy. (R)-ketamine is less sedating, produces fewer psychotomimetic or dissociative effects, and has lower abuse potential than (S)-ketamine. Its antidepressant mechanisms may involve NMDA receptor antagonism and non-NMDA receptor pathways. Further clinical research may lead to improved treatments for underserved neurological and psychiatric disorders.