Esketamine

Summary

Esketamine (CHEMBL395091) is an approved small-molecule analgesic (ATC N06AX27); indicated across 11 conditions including depressive disorder and toxic shock syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AX27 (+1 more)
• Indications: 11 conditions
• Clinical trials: 197
• Chemistry: 237.72 Da · C13H16ClNO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL395091
Name	Esketamine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	182137
ChEBI	CHEBI:60799
ATC	N06AX27, N01AX14
Molecular formula	C13H16ClNO
Molecular weight	237.72
InChIKey	YQEZLKZALYSWHR-ZDUSSCGKSA-N

SMILES: CN[C@@]1(CCCCC1=O)C2=CC=CC=C2Cl

IUPAC name: (2S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one

ChEBI definition: The S- (more active) enantiomer of ketamine.

Pharmacological roles (ChEBI): analgesic, NMDA receptor antagonist, intravenous anaesthetic.

Also known as: (-)-ketamine, Esketamina, Esketamine, Jnj-54135419, Keta-s, Ketamine s-isomer, Ketamine, (s)-, Ketamine, s-, Ketaved, L-ketamine, S-(-)-ketamine

Parent form; salt/anhydrous children: CHEMBL2364609

Patent coverage: 362 distinct patent families (958 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 615 (64%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Glutamate NMDA receptor; GRIN1/GRIN2A, Glutamate NMDA receptor, Sodium-dependent serotonin transporter, Kappa-type opioid receptor, Glutamate receptor ionotropic, NMDA 1.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 8 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
GRIN1	7.94	IC50	11.4	nM	CHEMBL_ACT_15767332
P35439	6.52	Ki	300	nM	CHEMBL_ACT_22482196
P35439	6.19	IC50	640	nM	CHEMBL_ACT_15718261
P35439	6.16	Ki	690	nM	CHEMBL_ACT_22482199
P35439	6.1	AC50	790	nM	CHEMBL_ACT_25120347
P35439	6.02	Ki	960	nM	CHEMBL_ACT_2638120

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
depressive disorder	4	MONDO:0002050	MONDO:0002050

5 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
toxic shock syndrome	3	MONDO:0001881	EFO:0006834
liver disorder	1	MONDO:0005154	EFO:0001421
drug dependence	1	MONDO:0005303	EFO:0003890
allergic rhinitis	1	MONDO:0011786	EFO:0005854
kidney disorder	1	MONDO:0005240	EFO:0003086

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 197.

Phase distribution

Phase	Trials
Not specified	74
PHASE4	59
PHASE1	25
PHASE3	14
PHASE2	10
EARLY_PHASE1	8
PHASE2/PHASE3	5
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04303325	PHASE4	RECRUITING	Effect of Esketamine on Postoperative Depression、Gut Microbiota、Bispectral Index Data of Depression Patients Undergoing Breast Cancer Operation (ESPOD-BI)
NCT05095857	PHASE4	RECRUITING	The Anaesthetic Ketamine as Treatment for Patients With Severe Acute Brain Injury
NCT05450432	PHASE4	RECRUITING	Long-Term Maintenance With Ketamine and Esketamine for Reduction of Suicide in High-Risk Patients With Depression
NCT05698394	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Low-dose Esketamine on Maternal Depression at 3 Years After Childbirth
NCT05826327	PHASE4	RECRUITING	Effects of Epidural Labor Analgesia With Esketamine on the Incidence of Postpartum Depression in Parturients
NCT05950646	PHASE4	RECRUITING	Mini-dose Dexmedetomidine-Esketamine Infusion and Perioperative Sleep Quality
NCT06062550	PHASE4	ACTIVE_NOT_RECRUITING	Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery
NCT06087510	PHASE4	RECRUITING	Different Dose Esketamine and Dexmedetomidine for Supplemental Analgesia and Longterm Outcomes
NCT06278779	PHASE4	RECRUITING	Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression
NCT06399185	PHASE4	RECRUITING	Effect of Dexmedetomidine and Esketamine on Catheter-related Bladder Discomfort
NCT06467513	PHASE4	RECRUITING	To Investigate the Effect of Esketamine Hydrochloride on Pulmonary Complications
NCT06822088	PHASE4	NOT_YET_RECRUITING	Effects of Esketamine on Oxygenation and Quality of Recovery in Patients Undergoing Thoracoscopic Surgery
NCT06853431	PHASE4	RECRUITING	Determination of ED50 and ED95 With Clinical Efficacy of Intranasal Dexmedetomidine Combined With Esketamine for Preoperative Sedation in Pediatric General Anesthesia
NCT06958393	PHASE4	NOT_YET_RECRUITING	Effect of Opioid-free Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Gastrointestinal Surgery
NCT07053345	PHASE4	RECRUITING	A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression
NCT07120477	PHASE4	NOT_YET_RECRUITING	Esketamine Versus Crisis Response Planning Versus Optimized Treatment as Usual for Suicide Prevention: A Pragmatic Controlled Trial in Two Brazilian Cities
NCT07179913	PHASE4	ACTIVE_NOT_RECRUITING	The Improvement of Low-dose Esketamine on Postoperative Depression in Patients Undergoing Bariatric Surgery With Preoperative Depression
NCT07308756	PHASE4	RECRUITING	Impact of Perioperative Dexmedetomidine and Esketamine on Postoperative Quality of Recovery
NCT07369102	PHASE4	RECRUITING	Esketamine With or Without Integration Therapy for Treatment-Resistant Depression
NCT07523334	PHASE4	NOT_YET_RECRUITING	Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients
NCT07556172	PHASE4	ACTIVE_NOT_RECRUITING	Clinical Study of Esketamine in Patients With Sepsis Undergoing Invasive Mechanical Ventilation
NCT07570160	PHASE4	NOT_YET_RECRUITING	Intranasal Dexmedetomidine or Esketamine for Negative Postoperative Behavioral Changes in Children
NCT00115102	PHASE4	COMPLETED	Sensory Examination and Pharmacological Modulation of Oral Hyperexcitability in Patients With Atypical Odontalgia and Matched Healthy Controls
NCT00209872	PHASE4	UNKNOWN	Optimal Multimodal Analgesia in Abdominal Hysterectomy
NCT00209885	PHASE4	UNKNOWN	Optimal Multimodal Analgesia in Laparoscopic Cholecystectomy
NCT00534586	PHASE4	COMPLETED	Anesthetics and Auditory, Visceral, and Heat Evoked Potentials
NCT02085577	PHASE4	COMPLETED	The Effect of Intraoperative Ketamine on Opioid Consumption and Pain After Spine Surgery in Opioid-dependent Patients
NCT02624401	PHASE4	COMPLETED	The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)
NCT02994173	PHASE4	COMPLETED	Dose-response of Ketamine in Patient Controlled Analgesia in Orthopaedic Surgery Patients
NCT03421275	PHASE4	UNKNOWN	Intranasal Esketamine and Fentanyl for Pain in Minor Trauma
NCT04459377	PHASE4	COMPLETED	Ketamine Analgesia in Third Molar Surgery
NCT04548973	PHASE4	COMPLETED	A Multicenter Study of the Efficacy and Safety of Esketamine for Analgesia During Cesarean Section
NCT04597320	PHASE4	COMPLETED	Esketamine Sedation and Fentanyl Sedation in Pediatric Dental Patients
NCT04599855	PHASE4	COMPLETED	A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
NCT04664530	PHASE4	UNKNOWN	The Study on the Esketamine in the Treatment of Postherpetic Neuralgia
NCT04682782	PHASE4	UNKNOWN	Intraoperative Small-dose Esketamine Infusion for Pain Control in Burn Patients
NCT04791059	PHASE4	COMPLETED	Low-dose S-ketamine and Dexmedetomidine in Combination With Opioids for Postoperative Analgesia
NCT04829318	PHASE4	COMPLETED	A Long-Term Extension Study for Participants With Treatment-resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment
NCT04964219	PHASE4	COMPLETED	Analgesic Effects of Low-dose S-ketamine in Major Spine Fusion Surgery
NCT05011214	PHASE4	UNKNOWN	Comparison of Sedation by Esketamine and Sevoflurane
NCT05229913	PHASE4	UNKNOWN	Effects of Esketamine on Postpartum Depression
NCT05289050	PHASE4	UNKNOWN	Analgesic Effect of Intraoperative Intravenous S-Ketamine During Total Knee Arthroplasty Surgery
NCT05299866	PHASE4	UNKNOWN	The Effect of S-ketamine Combined With Sufentanil for Postoperative Analgesia in Patients Following Cesarean Section
NCT05414006	PHASE4	COMPLETED	Effect of S-ketamine in Cesarean Section Combined Anesthesia
NCT05416073	PHASE4	UNKNOWN	Effect of Esketamine on Abdominal Pain During TACE-HAIC in Patients With Hepatocellular Carcinoma
NCT05458453	PHASE4	COMPLETED	An Exploratory Study of Esketamine in Patients After Thoracoscopic Surgery
NCT05506787	PHASE4	COMPLETED	The Effects of Intraoperative Esketamine on Postoperative Pain and Mood in Patients With Inflammatory Bowel Disease
NCT05515822	PHASE4	UNKNOWN	Use of Oxycodone in Bariatric Surgery
NCT05554627	PHASE4	WITHDRAWN	VA Aripiprazole vs Esketamine for Treatment Resistant Depression
NCT05670561	PHASE4	UNKNOWN	Effects of Esketamine on Acute Abdominal Pain After TACE in Patients With Hepatocellular Carcinoma
NCT05718544	PHASE4	COMPLETED	Mini-dose Esketamine-dexmedetomidine Supplemented Analgesia and Long-term Outcomes
NCT05732064	PHASE4	COMPLETED	Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality
NCT05922605	PHASE4	UNKNOWN	Analgesic Effects of Caudal S-ketamine for Supplementation of Ropivacaine Caudal Analgesia in Children With Hypospadias
NCT05925283	PHASE4	UNKNOWN	Clinical Study of Oral Midazolam Combined With Esketamine Administered Intranasally for Pediatric Preoperative Sedation
NCT06398834	PHASE4	COMPLETED	Esketamine and Butorphanol for Post-Lobectomy Pain
NCT06566469	PHASE4	COMPLETED	Dexmedetomidine-esketamine Combined Nasal Administration and Emergence Delirium
NCT06574945	PHASE4	COMPLETED	Anesthesia for Loop Electrosurgical Excision Procedure (LEEP).
NCT06613243	PHASE4	COMPLETED	Different Doses of Dexmedetomidine Combined With Esketamine in Women Undergoing Cesarean Delivery
NCT06853041	PHASE4	COMPLETED	ESKetamine Low-dose vs Ketamine Low-dose for Severe Acute Pain in Emergency Units, Comparison of PsychodyslEptic Effects
NCT06051227	PHASE3	RECRUITING	Fentanyl or Esketamine for Traumatic PAIN (FORE-PAIN) Trial
NCT07227454	PHASE3	RECRUITING	A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder
NCT01022840	PHASE3	COMPLETED	The Preemptive Analgetic Potency of Low Dose S-Ketamine
NCT01275547	PHASE2/PHASE3	COMPLETED	The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam
NCT02417064	PHASE3	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression
NCT02418585	PHASE3	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression
NCT02422186	PHASE3	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants With Treatment-resistant Depression
NCT02493868	PHASE3	COMPLETED	A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
NCT03039192	PHASE3	COMPLETED	54135419SUI3001: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide
NCT03097133	PHASE3	COMPLETED	54135419SUI3002: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide
NCT03434041	PHASE3	COMPLETED	A Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression
NCT03852160	PHASE3	WITHDRAWN	A Study of Esketamine Nasal Spray Plus a New Standard-of-care Oral Antidepressant or Placebo Nasal Spray Plus a New Standard-of-care Oral Antidepressant in Adult and Elderly Participants With Treatment-resistant Depression
NCT04338321	PHASE3	COMPLETED	A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder
NCT04425473	PHASE2/PHASE3	COMPLETED	Esketamine and Perioperative Depressive Symptoms
NCT04476446	PHASE3	COMPLETED	An Expanded Access Protocol for Esketamine Treatment in Participants With Treatment Resistant Depression (TRD) Who do Not Have Other Treatment Alternatives
NCT05096468	PHASE2/PHASE3	COMPLETED	Esketamine Combined With Pregabalin on Acute Postoperative Pain in Patients Undergoing Resection of Spinal Neoplasms.
NCT05160493	PHASE2/PHASE3	COMPLETED	The Effect of Esketamine Combined With Pregabalin on Chronic Postsurgical Pain in Patients After Craniotomy.
NCT05839366	PHASE3	UNKNOWN	Adjunctive Esketamine for Analgesia in Mechanically Ventilated Septic Shock Patients
NCT06117917	PHASE2/PHASE3	UNKNOWN	Esketamine Combined With Pregabalin on CPSP in Spinal Patients.
NCT06920576	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Effects of Esketamine Versus Magnesium Sulfate on Emotional State and Postoperative Pain in Patients Undergoing Nasal Endoscopic Surgery
NCT07131033	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Esketamine Combined With Magnesium Sulfate for Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy
NCT07317206	PHASE2	RECRUITING	Ayahuasca, Esketamine and PTSD
NCT01640080	PHASE2	COMPLETED	A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression
NCT01998958	PHASE2	COMPLETED	A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression
NCT02133001	PHASE2	COMPLETED	A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide
NCT03185819	PHASE2	COMPLETED	Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Participants Assessed to be at Imminent Risk for Suicide
NCT03231683	PHASE2	COMPLETED	Use of S+Ketamine During Target-Controlled Intravenous Anaesthesia After Abdominal Hysterectomy
NCT05092152	PHASE2	COMPLETED	Propofol Versus Ketamine for Rapid Sequence Intubation in Critically Ill Patients
NCT05635955	PHASE2	COMPLETED	Remimazolam Versus Propofol for Painless Abortion
NCT06633315	PHASE2	COMPLETED	Esketamine Combined With Dexmedetomidine Sedation in Head MRI Examination of Children With Autism Spectrum Disorder
NCT07212946	PHASE2	COMPLETED	Ayahuasca and Esketamine for Major Depression
NCT01780259	PHASE1	COMPLETED	A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants
NCT01980303	PHASE1	COMPLETED	A Study to Assess the Pharmacokinetics of Intranasally Administered Esketamine in Healthy Japanese and Caucasian Volunteers
NCT02060929	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics of Intranasal Esketamine Administered With and Without a Nasal Guide on the Intranasal Device
NCT02094378	PHASE1	COMPLETED	A Study to Evaluate the Effect of Intranasal Esketamine on Cognitive Functioning in Healthy Subjects
NCT02129088	PHASE1	COMPLETED	A Pharmacokinetic, Safety and Tolerability Study of Esketamine in Healthy Elderly and Adult Participants
NCT02154334	PHASE1	COMPLETED	Study to Assess the Effects of Allergic Rhinitis and Co-administration of Mometasone or Oxymetazoline on the Pharmacokinetics, Safety, and Tolerability of Intranasal Esketamine
NCT02228239	PHASE1	COMPLETED	Study to Assess the Effects of Esketamine on Safety of On-road Driving in Healthy Participants
NCT02343289	PHASE1	COMPLETED	A Study to Evaluate the Absolute Bioavailability of Intranasal and Oral Esketamine and the Effects of Clarithromycin on the Pharmacokinetics of Intranasal Esketamine in Healthy Participants
NCT02345148	PHASE1	COMPLETED	Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Elderly and and Healthy Younger Adult Participants
NCT02568176	PHASE1	COMPLETED	Pharmacokinetic Study of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Participants

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).