prof. dr hab. Andrzej Pilc
Key words: ketamine, S-ketamine, antidepressant effect, NMDA receptor
Esketamine is the (S)(+) isomer of ketamine, both of them belong to the group of psychedelics. Ketamine was first used as a general anesthetic. Later, its mechanism of action was discovered, which is the blockade of NMDA receptors for glutamate. Blocking this receptor has also been reported in preclinical studies to produce antidepressant effects in animals. In 2000, rapid, antidepressant effect of ketamine in humans was described, appearing as early as 75 minutes after administration of the drug.
Since the S-isomer blocks the NMDA receptor at lower doses than ketamine, its effects have been investigated. It turns out that the agent has a strong antidepressant effect after just one dose. The nasal form of this esketamine was approved by the Food and Drug Administration (FDA) in 2019 for the treatment-resistant depression (TRD). However, the substance must be administered in medical facilities, due to its numerous adverse effects, such as dissociative effects, anxiety, sedation, dizziness, and the patient has to remain under observation for 1.5–2 hours.