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|Trade names||Ketanest S|
|AHFS/Drugs.com||Consumer Drug Information|
|Chemical and physical data|
|Molar mass||237.725 g/mol|
|3D model (Jmol)|
|(what is this?)|
Esketamine (also (S)-ketamine or S(+)-ketamine) (brand name Ketanest S) is a general anaesthetic and a dissociative. It is the S(+) enantiomer of the drug ketamine, a general anaesthetic. Esketamine acts primarily as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, but is also a dopamine reuptake inhibitor. As of August 18, 2016, it is in phase III clinical trials for treatment-resistant depression (TRD).
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.
However a number of studies have suggested the contrary ("R ketamine appears to be a potent and safe antidepressant relative to S ketamine", "(2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine", "R-ketamine as a longer-lasting antidepressant compared with rapastinel" ).
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. This is however in contradiction with R-ketamine being devoid of psychotomimetic side effects.
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, another study found no difference between racemic and (S)-ketamine on the patient's level of vigilance. Interpretation of this finding is complicated by the fact that racemic ketamine comprises 50% (S)-ketamine.
A 2013 study in mice found that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine in mice.
As of 2016 Johnson & Johnson was developing a nasal spray formulation of esketamine as a treatment for depression for people that have been unresponsive to other antidepressants and phase III clinical trials of were underway.
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