Is (R)-ketamine a Potential Therapeutic Agent for Treatment-Resistant Depression with Less Detrimental Side Effects? A Review of Molecular Mechanisms Underlying Ketamine and its Enantiomers.
Biochemical Pharmacology February 1, 2022 Ellen Scotton, Bárbara Antqueviezc, Mailton Vasconcelos et al. 35 citations
About one-third of people with major depressive disorder do not respond to standard antidepressants, and even those who do respond may wait weeks for effects. Ketamine, a mixture of two enantiomers, (R)-ketamine and (S)-ketamine, blocks NMDARs and shows rapid antidepressant effects in treatment-resistant depression. Preclinical evidence indicates (R)-ketamine has lower NMDAR affinity but greater and longer-lasting antidepressant potency with fewer side effects than racemic ketamine or (S)-ketamine. Ketamine and its enantiomers also modulate synaptogenesis and neurotransmission. This review summarizes current evidence on neurotransmission, neuroplasticity, and neural network activity as mechanisms, highlighting intracellular signaling pathways involving mTOR, ERK, and BDNF, and discusses probable mechanisms behind side effects.