On the Eve of Upgrading Antidepressants: (R)-Ketamine and Its Metabolites

Mechanistic Target of Rapamycin–Independent Antidepressant Effects of ( R )-Ketamine in a Social Defeat Stress Model

“…Furthermore, a single bilateral infusion of (R)-ketamine into the infralimbic cortex of the medial prefrontal cortex (PFC) and the cornu ammonis 3 (CA3) and dentate gyrus (DG) of the hippocampus demonstrates antidepressant effects (35), suggesting that these brain regions play a role in the direct antidepressant actions of (R)-ketamine. Unlike (S)-ketamine, (R)-ketamine appears to be independent of psychotomimetic side effects and abuse potential (32,(36)(37)(38).…”

Special Topic on Mental Health and Addiction

“…Compared with (S)-ketamine, the (R)-ketamine enantiomer has greater and longer-lasting antidepressant efficacy in several animal models of depression, such as the forced swim test, learned helplessness, and chronic social defeat stress. However, because of inconsistencies with previous studies and controversy regarding the antidepressant actions of ketamine metabolites independent of NMDA receptor inhibition, this conclusion should be treated with caution, and it needs further investigation and verification [18].…”

Drug addiction: a curable mental disorder?

“…It is especially intriguing that subanesthetic ketamine has been shown to possess rapid antidepressant effects in both preclinical and clinical studies [35][36][37]. Abundant epidemiological data have revealed high comorbidity of drug addiction and major depression [38]; therefore, the above results suggest that subanesthetic ketamine could be especially effective to treat the comorbidity of drug addiction and depression [39]. Besides directly modulating the ionotropic glutamate receptors, recent studies have demonstrated promising effects for the use of allosteric modulators of mGluRs in drug addiction [40].…”