Esketamine is approximately twice as potent as racemic ketamine. It is eliminated from the human body more quickly than arketamine (R(–)-ketamine) or racemic ketamine, although arketamine slows its elimination.
A number of studies have suggested that esketamine has a more medically useful pharmacological action than arketamine or racemic ketamine. Esketamine inhibits dopamine transporters eight times more than arketamine. 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 arketamine. Unlike arketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while arketamine 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 arketamine is reportedly more relaxing. However, other studies have found no difference between the isomers in the patient's level of vigilance.
Although most studies suggest that esketamine is preferable for medical uses, a 2013 study found that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine in mice.
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