(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

被引:2
|
作者
Shafique, Hana [1 ]
Demers, Julie C. [2 ]
Biesiada, Julia [2 ]
Golani, Lalit K. [3 ]
Cerne, Rok [4 ]
Smith, Jodi L. [4 ]
Szostak, Marta [5 ]
Witkin, Jeffrey M. [4 ,6 ,7 ]
机构
[1] Duke Univ, Sch Med, Durham, NC 27710 USA
[2] Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA
[3] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA
[4] Ascens St Vincent Hosp, Lab Antiepilept Drug Discovery, Indianapolis, IN 46260 USA
[5] SWPS Univ, Dept Psychol, PL-03815 Warsaw, Poland
[6] Ascens St Vincent Hosp, Dept Neurosci, Indianapolis, IN 46260 USA
[7] Ascens St Vincent Hosp, Dept Trauma Res, Indianapolis, IN 46260 USA
关键词
major depressive disorder; rapid-acting antidepressant; inflammation; ketamine; (R)-ketamine; substance use disorder; D-ASPARTATE ANTAGONIST; HEALTHY-VOLUNTEERS; SEX-DIFFERENCES; ANTIDEPRESSANT; KETAMINE; (R)-KETAMINE; RECEPTOR; PHARMACOLOGY; PSYCHOPATHOLOGY; (S)-KETAMINE;
D O I
10.3390/ijms25126804
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:18
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