Esketamine is approximately twice as potent as racemic ketamine. Esketamine 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 psychedelic or hallucinatory effect while R(-)-ketamine is reported to be more relaxing. However, other studies have found no difference between the isomers in the patient's level of vigilance.
Johnson & Johnson is developing a nasal spray formulation of esketamine as a treatment for depression in patients that have been unresponsive to other antidepressants. As of July 2013, Phase 1 clinical trial of intranasal esketamine sponsored by the Johnson & Johnson subsidiary Janssen Pharmaceutica is underway with 58 participants in Belgium.AstraZeneca (AZN) is studying lanicemine, and Naurex Inc. and Cerecor Inc. are also in the process of developing new antidepressant drugs that act similarly to ketamine.
^ abHimmelseher, S.; Pfenninger, E. (2008). "Die klinische Anwendung von S-(+)-Ketamin - eine Standortbestimmung". AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie33 (12): 764–770. doi:10.1055/s-2007-994851. PMID9893910.edit
^Ihmsen, H.; Geisslinger, G.; Schüttler, J. (2001). "Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine". Clinical pharmacology and therapeutics70 (5): 431–438. doi:10.1067/mcp.2001.119722. PMID11719729.edit
^ abDoenicke, A.; Kugler, J.; Mayer, M.; Angster, R.; Hoffmann, P. (1992). "Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings". Der Anaesthesist41 (10): 610–618. PMID1443509.edit
^Pfenninger, E.; Baier, C.; Claus, S.; Hege, G. (1994). "Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses". Der Anaesthesist. 43 Suppl 2: S68–S75. PMID7840417.edit
^ abVollenweider, F. X.; Leenders, K. L.; Oye, I.; Hell, D.; Angst, J. (1997). "Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)". European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology7 (1): 25–38. doi:10.1016/S0924-977X(96)00042-9. PMID9088882.edit