Esketamine

Esketamine

Systematic (IUPAC) name
(S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone
Clinical data
Trade names	Ketanest S
AHFS/Drugs.com	Consumer Drug Information
Identifiers
CAS Number	33643-46-8 N
ATC code	N01AX14 (WHO)
PubChem	CID: 182137
DrugBank	DB01221 Y
ChemSpider	158414 N
UNII	50LFG02TXD Y
ChEBI	CHEBI:6121 Y
ChEMBL	CHEMBL742 Y
Chemical data
Formula	C13H16ClNO
Molecular mass	237.725 g/mol
SMILES CN[C@](C1=C(Cl)C=CC=C1)(CCCC2)C2=O
InChI InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3/t13-/m0/s1 N Key:YQEZLKZALYSWHR-ZDUSSCGKSA-N N
NY (what is this?)  (verify)

Main article: Ketamine

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 NMDA receptor antagonist, but is also a dopamine reuptake inhibitor. As of July 2014, it is in phase II clinical trials for treatment-resistant depression (TRD).

Pharmacology

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, 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.

Potential use as an antidepressant

Main article: Ketamine § Antidepressant use

Johnson & Johnson is developing a nasal spray formulation of esketamine as a treatment for depression in patients that have been unresponsive to other antidepressants in the United States. As of July 2014, phase II clinical trials of intranasal esketamine sponsored by the Johnson & Johnson subsidiary Janssen Pharmaceutica are underway. Other pharmaceutical companies are also developing new antidepressant drugs that act similarly to ketamine, including Naurex's rapastinel (GLYX-13) and NRX-1074, Cerecor's CERC-301, and VistaGen's AV-101.

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.

See also

• ALKS-5461
• CERC-501
• NSI-189
• AV-101