%0 Journal Article
%T (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders.
%A Shafique H
%A Demers JC
%A Biesiada J
%A Golani LK
%A Cerne R
%A Smith JL
%A Szostak M
%A Witkin JM
%J Int J Mol Sci
%V 25
%N 12
%D 2024 Jun 20
%M 38928508
%F 6.208
%R 10.3390/ijms25126804
%X NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.