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Arketamine hydrochloride (HS-10519) is the (R)-enantiomer of the racemic anesthetic ketamine, currently under development as a rapid-acting antidepressant. Unlike esketamine (the S-enantiomer), which is a potent N-methyl-D-aspartate (NMDA) receptor antagonist, arketamine exhibits lower affinity for the NMDA receptor but has shown potent and long-lasting antidepressant-like effects in preclinical models, potentially with a superior safety profile regarding dissociative and psychotomimetic side effects. Its mechanism of action is thought to involve the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the brain-derived neurotrophic factor (BDNF)-mTOR signaling pathway. HS-10519 is specifically being investigated for major depressive disorder (MDD) in patients with acute suicidal ideation or behavior.
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