| Autor: |
Shafique H; Duke University School of Medicine, Durham, NC 27710, USA., Demers JC; Indiana University-Purdue University, Indianapolis, IN 46202, USA., Biesiada J; Indiana University-Purdue University, Indianapolis, IN 46202, USA., Golani LK; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA., Cerne R; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN 46260, USA., Smith JL; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN 46260, USA., Szostak M; Department of Psychology, SWPS University, 03-815 Warsaw, Poland., Witkin JM; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN 46260, USA.; Departments of Neuroscience and Trauma Research, Ascension St. Vincent Hospital, Indianapolis, IN 46260, USA. |
| Abstrakt: |
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. |
