Ketamine

Ketamine is a dissociative anesthetic in the arylcyclohexylamine class, used for anesthesia and analgesia. It is sold as a racemic mixture of R- and S-enantiomers; the S-enantiomer, esketamine, is marketed separately for some indications. Ketamine has rapid onset and dissociative properties that distinguish it from many other anesthetics.

Mechanism: Ketamine primarily blocks NMDA receptors, reducing excitatory glutamatergic activity. It also interacts with opioid receptors and other signaling pathways, contributing to analgesia and mood effects. The exact mechanism of its rapid antidepressant action is not fully understood, but NMDA receptor modulation and downstream synaptic changes are implicated.

Medical uses: In anesthesia, ketamine provides induction and maintenance with preserved airway reflexes and cardiovascular stability and is used in pain management and procedural sedation. Esketamine nasal spray has been approved for treatment-resistant depression and certain depressive episodes under medical supervision, reflecting renewed interest in its rapid-acting antidepressant properties.

Safety and regulation: Ketamine can elevate blood pressure and heart rate, cause dissociation and perceptual changes, and has potential for misuse and dependence. Chronic high-dose use is linked to urinary symptoms and cystitis. It is a controlled substance in many countries, with usage restricted to supervised settings to minimize risks.