Activation of σ1-Receptors by R-Ketamine May Enhance the Antidepressant Effect of S-Ketamine
Biomedicines September 28, 2023 Hans O. Kalkman 8 citations
Ketamine is a racemic mixture of S-ketamine and R-ketamine, each with distinct pharmacological activities. S-ketamine blocks NMDA channels and acts as an opioid μ-receptor agonist, while R-ketamine binds to σ1-receptors and is believed to act as an agonist. In patients with major depressive disorder, S-ketamine nasal spray shows clear antidepressant activity, but compared to intravenous racemic ketamine, its response rate, duration of action, and anti-suicidal activity appear less pronounced. The σ1-activity of R-ketamine may enhance pathways through which S-ketamine produces antidepressant effects and provide its own antidepressant activity, potentially explaining the superior effect of racemic ketamine over S-ketamine alone.