General
Preferred name
esketamine
Synonyms
ESKETAMINE HYDROCHLORIDE ()
AM-101 ()
Spravato ()
Ketanest s ()
Ketamine hydrochloride, (s)- ()
Ketamine hydrochloride, s- ()
S-(-)-ketamine ()
Jnj-54135419 ()
S-ketamine ()
Ketamine, (s)- ()
(-)-ketamine ()
Ketamine, s- ()
Keta-s ()
Ketaved ()
L-ketamine ()
(S)-Ketamine (hydrochloride) ()
(S)-Ketamine (hydrochloride) (CRM) ()
(S)-Ketamine (hydrochloride) ()
P&D ID
PD050157
CAS
33643-46-8
33643-47-9
Tags
natural product
drug
available
Approved by
EMA
FDA
First approval
2019
Drug Status
investigational
approved
Drug indication
Depression
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
As the ketamine S enatiomer esketamine is twice as potent and has a more medically useful pharmacological action than the racemate racemate. Part of this advantage arises from inhibition of dopamine transporters.
ROE
Less than 1% of a dose of nasal esketamine is measured as unchanged drug, excreted in the urine. Following intravenous (IV) or oral (PO) administration, esketamine-derived metabolites were mainly recovered in urine (⥠78% of a radiolabeled dose), and a smaller percentage was measured in the feces (⤠2% of a radiolabeled dose) [FDA label].
INDICATION
This drug is indicated in conjunction with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults [FDA label]. Note: Esketamine is not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established to this date [FDA label].
HALF-LIFE
The mean terminal half-life (t1/2) ranges from 7 to 12 hours [FDA label].
MOA
Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The exact mechanism by which esketamine acts as an antidepressant is unknown. The primary circulating metabolite of esketamine (_noresketamine_) shows activity at the same receptor with a weaker affinity [FDA label].
METABOLISM
Esketamine is mainly metabolized to the _noresketamine_ metabolite by cytochrome P450 (CYP) enzymes, CYP2B6 and CYP3A4, and to a lesser extent, CYP2C9 and CYP2C19. Noresketamine is metabolized by cytochrome-dependent metabolic pathways followed by subsequent glucuronidation of metabolites [FDA label].
ABSORPTION
Due to the fact that this drug is administered via nasal spray, absorption is rapid. The mean absolute bioavailability is approximately 48% after esketamine nasal spray administration. The time to achieve peak esketamine plasma concentration is 20 to 40 minutes after the last nasal spray of esketamine. Inter-subject variability of esketamine ranges from 27% to 66% for Cmax (maximum concentration) and 18% to 45% for AUC (area under the curve). The intra-subject variability of esketamine is about 15% for Cmax and 10% for AUC [FDA label].
MOA
Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The exact mechanism by which esketamine acts as an antidepressant is unknown. The primary circulating metabolite of esketamine (_noresketamine_) shows activity at the same receptor with a weaker affinity [FDA label]. ;
INDICATION
This drug is indicated in conjunction with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults [FDA label].; ; Note: Esketamine is not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established to this date [FDA label].
DESCRIPTION
As the ketamine (S) enatiomer esketamine is twice as potent and has a more medically useful pharmacological action than racemic . Part of this advantage arises from inhibition of dopamine transporters.
(GtoPdb)
PHARMACODYNAMICS
**General effects** Esketamine is considered a central nervous system (CNS) depressant agent. It may cause sedation, dizziness, and lethargy, among other symptoms [FDA Label]. This drug has dissociative and antidepressant properties [FDA label]. Acutely, esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Two placebo-controlled studies were performed to evaluate the effects of ketamine on the ability to drive. The effects of esketamine 84 mg were comparable to placebo at 6 hours and 18 hours post ingestion [FDA label]. **Effects on cardiac electrophysiology** The effect of esketamine (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was studied in a randomized, double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), 4-period, crossover study in 60 healthy volunteers. A marked increase in heart rate (higher than 10 bpm) was measured in subjects receiving intranasal and intravenous esketamine. Summative evidence from both nonclinical and clinical data suggests a lack of clinically relevant QTc prolongation at the normal therapeutic dose of esketamine [FDA label]. **Effects on blood pressure** Eskestamine causes increases in systolic and/or diastolic blood pressure at all therapeutic doses. Peak blood pressure elevation after esketamine administration occurs about 40 minutes after administration and lasts approximately 4 hours [FDA label]. **Cognitive effects** In a study of healthy volunteers, one dose of this agent caused decline in cognitive performance 40 minutes after administration. Compared to subjects ingesting a placebo, esketamine-treated subjects required a higher level of effort to complete assigned cognitive tests at 40 minutes after administration. Cognitive performance and mental effort were found to be similar between esketamine and placebo at 2 hours after administration [FDA label]. Reports of long-term memory or cognitive impairment have been made following repeated ketamine misuse or abuse. No adverse effects of esketamine nasal spray on cognitive function were seen in a one-year open-label safety study. The long-term cognitive effects of esketamine have not been studied for more than a 1 year period, therefore, the risk of cognitive decline with long-term use is not yet confirmed [FDA label].
PHARMACODYNAMICS
**General effects**; ; Esketamine is considered a central nervous system (CNS) depressant agent. It may cause sedation, dizziness, and lethargy, among other symptoms [FDA Label]. This drug has dissociative and antidepressant properties [FDA label]. Acutely, esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Two placebo-controlled studies were performed to evaluate the effects of ketamine on the ability to drive. The effects of esketamine 84 mg were comparable to placebo at 6 hours and 18 hours post ingestion [FDA label].; ; **Effects on cardiac electrophysiology**; ; The effect of esketamine (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was studied in a randomized, double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), 4-period, crossover study in 60 healthy volunteers. A marked increase in heart rate (higher than 10 bpm) was measured in subjects receiving intranasal and intravenous esketamine. Summative evidence from both nonclinical and clinical data suggests a lack of clinically relevant QTc prolongation at the normal therapeutic dose of esketamine [FDA label]. ; ; **Effects on blood pressure**; ; Eskestamine causes increases in systolic and/or diastolic blood pressure at all therapeutic doses. Peak blood pressure elevation after esketamine administration occurs about 40 minutes after administration and lasts approximately 4 hours [FDA label]. ; ; **Cognitive effects**; ; In a study of healthy volunteers, one dose of this agent caused decline in cognitive performance 40 minutes after administration. Compared to subjects ingesting a placebo, esketamine-treated subjects required a higher level of effort to complete assigned cognitive tests at 40 minutes after administration. Cognitive performance and mental effort were found to be similar between esketamine and placebo at 2 hours after administration [FDA label].; ; Reports of long-term memory or cognitive impairment have been made following repeated ketamine misuse or abuse. No adverse effects of esketamine nasal spray on cognitive function were seen in a one-year open-label safety study. The long-term cognitive effects of esketamine have not been studied for more than a 1 year period, therefore, the risk of cognitive decline with long-term use is not yet confirmed [FDA label].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
10
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
Guide to Pharmacology
NCATS Inxight Approved Drugs
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
41
Molecular Weight
237.09
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
1
Rotatable Bonds
2
Ring Count
2
Aromatic Ring Count
1
cLogP
2.9
TPSA
29.1
Fraction CSP3
0.46
Chiral centers
1.0
Largest ring
6.0
QED
0.86
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Source data
