Esketamine is approximately twice as potent as racemic ketamine. It is eliminated from the human body more quickly than R(−)-ketamine or racemic ketamine, although R(−)-ketamine slows its elimination.
A number of studies have suggested that esketamine has a more medically useful pharmacological action than R(−)-ketamine or racemic ketamine. Esketamine inhibits dopamine transporters eight times more than R(−)-ketamine. This increases dopamine activity in the brain. At doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients. Patients also generally recover mental function more quickly after being treated with pure esketamine, which may be a result of the fact that it is cleared from their system more quickly.
Esketamine has an affinity for the PCP binding site of the NMDA receptor 3-4 times higher than that of R(−)-ketamine. Unlike R(−)-ketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while R(−)-ketamine decreases glucose metabolism in the brain. This difference may be responsible for the fact that esketamine generally has a more dissociative or hallucinogenic effect while R(−)-ketamine is reportedly more relaxing. However, other studies have found no difference between the isomers in the patient's level of vigilance.
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