(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders.
International journal of molecular sciences – June 20, 2024
Source: PubMed
Summary
A promising breakthrough in mental health treatment shows that (R)-ketamine may offer relief for depression without the typical side effects of traditional ketamine therapy. This variant works as a rapid-acting antidepressant for major depressive disorder, while causing less sedation and having lower abuse potential than its counterpart. Research demonstrates effectiveness across multiple psychiatric conditions, with positive results in treating both depression and neurological disorders. The compound appears to reduce inflammation and shows potential for helping substance use disorder patients.
Abstract
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.