S-ketamine (Esketamine)

S-ketamine (esketamine) is a purified form of ketamine that contains only the S-enantiomer, which is the more active component of the molecule in terms of clinical effects. It is a prescription medication used mainly in controlled medical settings. Esketamine is primarily used for the treatment of treatment-resistant depression and, in some cases, acute depressive symptoms with suicidal thoughts. It is often administered as a nasal spray under strict medical supervision in clinics. It works by affecting the brain’s glutamate system (NMDA receptors), which can help rapidly improve mood and emotional regulation in some patients, sometimes within hours or days. the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L‑type calcium chanels have also been described. S(+)-ketamine stimulates the sympathetic nerve system, making it an ideal drug for analgosedation or induction of anesthesia in instable patients.

Common effects during treatment may include temporary dissociation, dizziness, mild sedation, or changes in perception. Because of these effects, patients are monitored by healthcare professionals during and after administration. Esketamine (S‑Ketamine) is the pharmacologically active S‑enantiomer of ketamine, marketed as Spravato® in a nasal spray formulation. It is FDA-approved for treatment-resistant depression (TRD) and major depressive disorder with acute suicidal ideation, and as of early 2025 can now be used without concurrent oral antidepressants . Delivered in tightly regulated medical setting sessions, each dose is administered under clinical supervision due to risks such as dissociation, sedation, and elevated blood pressure. Patients must be monitored for at least two hours post-administration, and the drug is dispensed only through accredited providers under the Spravato REMS program Drugs.com+1Verywell Mind+1.