KETAMINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H16ClNO
Molecular Weight	237.725
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC1(CCCCC1=O)C2=CC=CC=C2Cl

InChI

InChIKey=YQEZLKZALYSWHR-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23432384

Ketamine (brand name Ketalar) is a cyclohexanone derivative used for induction of anesthesia. Ketalar is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation; also, it is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents. Ketamine blocks NMDA receptors through an interaction with sites thought to be located within the ion channel pore region. However, the complete pharmacology of ketamine is more complex, and it is known to directly interact with a variety of other sites to varying degrees. Recently, it was shown that inclusion of the NR3B subunit does not alter the ketamine sensitivity of recombinant NR1/NR2 receptors expressed in oocytes. Likewise, 100 μM ketamine produced only weak inhibition of the glycine-induced current of NR1/NR3A/NR3B receptors. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Ketamine was first synthesized in 1962 by Calvin Stevens at Parke-Davis Co (now Pfizer) as an alternative anesthetic to phencyclidine. It was first used in humans in 1965 by Corssen and Domino and was introduced into clinical practice by 1970.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2858237	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf	Primary		Approved 8429	KETALAR Approved Use Ketamine hydrochloride injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine hydrochloride is best suited for short procedures but it can be used, with additional doses, for longer procedures. Ketamine hydrochloride injection is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents. Ketamine hydrochloride injection is indicated to supplement low-potency agents, such as nitrous oxide. Specific areas of application are described in the CLINICAL PHARMACOLOGY Section. Launch Date 1970

C_max

Value	Dose	Analyte	Population
2104 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg/kg single, nasal dose: 9 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
496 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	3 mg/kg single, nasal dose: 3 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
632 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg single, rectal dose: 9 mg route of administration: Rectal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
148.3 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
163.6 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg/kg single, nasal dose: 9 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
76.4 mg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	3 mg/kg single, nasal dose: 3 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
111.2 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg single, rectal dose: 9 mg route of administration: Rectal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
125 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
120 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg/kg single, nasal dose: 9 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
123 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	3 mg/kg single, nasal dose: 3 mg/kg route of administration: Nasal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
100 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881626/	9 mg single, rectal dose: 9 mg route of administration: Rectal experiment type: SINGLE co-administered:	KETAMINE plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.5 mg/kg 1 times / day single, intravenous Studied dose Dose: 0.5 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.5 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29501990/	unhealthy, 18-65 years n = 126 Health Status: unhealthy Condition: major depressive disorder \| bipolar disorder Age Group: 18-65 years Sex: M+F Population Size: 126 Sources: https://pubmed.ncbi.nlm.nih.gov/29501990/	Other AEs: Dissociation... Other AEs: Dissociation Sources: https://pubmed.ncbi.nlm.nih.gov/29501990/
14 mg 8 times / day single, intranasal Highest studied dose Dose: 14 mg, 8 times / day Route: intranasal Route: single Dose: 14 mg, 8 times / day Sources: https://www.ema.europa.eu/en/documents/product-information/spravato-epar-product-information_en.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000OtherR.pdf	healthy, adult n = 34 Health Status: healthy Age Group: adult Sex: M Population Size: 34 Sources: https://www.ema.europa.eu/en/documents/product-information/spravato-epar-product-information_en.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000OtherR.pdf	Other AEs: Dizziness, Hyperhidrosis... Other AEs: Dizziness Hyperhidrosis Somnolence Hypoaesthesia Feeling abnormal Nausea Vomiting Sources: https://www.ema.europa.eu/en/documents/product-information/spravato-epar-product-information_en.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000OtherR.pdf
50 mg single, intranasal Dose: 50 mg Route: intranasal Route: single Dose: 50 mg Sources: https://clinicaltrials.gov/ct2/show/NCT01304147	unhealthy n = 19 Health Status: unhealthy Condition: Treatment-Resistant Depression Population Size: 19 Sources: https://clinicaltrials.gov/ct2/show/NCT01304147	Other AEs: Numbness, Blurred vision... Other AEs: Numbness (below serious, 2 patients) Blurred vision (below serious, 1 patient) Decreased appetite (below serious, 1 patient) Irritable (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01304147
0.1 mg/kg single, intravenous Dose: 0.1 mg/kg Route: intravenous Route: single Dose: 0.1 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	unhealthy n = 18 Health Status: unhealthy Condition: Treatment-Resistant Depression Population Size: 18 Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	Other AEs: Headache, Nausea... Other AEs: Headache (below serious, 3 patients) Nausea (below serious, 2 patients) Vomiting (below serious, 1 patient) Depression (below serious, 1 patient) Diarrhea (below serious, 1 patient) Insomnia (below serious, 1 patient) Pain in extremity (below serious, 1 patient) Poor quality sleep (below serious, 1 patient) Suicidal ideation (below serious, 1 patient) Flushing (below serious, 1 patient) Hot flush (below serious, 1 patient) Increased appetite (below serious, 1 patient) White blood cell count decreased (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01920555
0.2 mg/kg single, intravenous Dose: 0.2 mg/kg Route: intravenous Route: single Dose: 0.2 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	unhealthy n = 20 Health Status: unhealthy Condition: Treatment-Resistant Depression Population Size: 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	Other AEs: Suicide attempt, Headache... Other AEs: Suicide attempt (serious, 1 patient) Headache (below serious, 2 patients) Vomiting (below serious, 1 patient) Depression (below serious, 1 patient) Dyspepsia (below serious, 2 patients) Tachycardia (below serious, 1 patient) Asthenia (below serious, 1 patient) Dermatitis contact (below serious, 1 patient) Fall (below serious, 1 patient) Hepatic enzyme increased (below serious, 1 patient) Loss of consciousness (below serious, 1 patient) Malaise (below serious, 1 patient) Overdose (below serious, 1 patient) Presyncope (below serious, 1 patient) Viral upper respiratory tract infection (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01920555
0.5 mg/kg single, intravenous Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	unhealthy n = 22 Health Status: unhealthy Condition: Treatment-Resistant Depression Population Size: 22 Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	Other AEs: Headache, Nausea... Other AEs: Headache (below serious, 1 patient) Nausea (below serious, 3 patients) Vomiting (below serious, 1 patient) Depression (below serious, 1 patient) Diarrhea (below serious, 1 patient) Pain in extremity (below serious, 1 patient) Suicidal ideation (below serious, 1 patient) Tooth abscess (below serious, 1 patient) Cough (below serious, 1 patient) Respiratory tract infection (below serious, 1 patient) Vertigo (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01920555
0.5 mg/kg single, oral Dose: 0.5 mg/kg Route: oral Route: single Dose: 0.5 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01680172	unhealthy n = 3 Health Status: unhealthy Condition: Depression and Anxiety\|Cancer Population Size: 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01680172	Other AEs: Headache, Chest pain... Other AEs: Headache (below serious, 2 patients) Chest pain (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01680172
1 mg/kg single, intravenous Dose: 1 mg/kg Route: intravenous Route: single Dose: 1 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	unhealthy n = 20 Health Status: unhealthy Condition: Treatment-Resistant Depression Population Size: 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01920555	Other AEs: Headache, Nausea... Other AEs: Headache (below serious, 3 patients) Nausea (below serious, 3 patients) Vomiting (below serious, 1 patient) Blood pressure increased (below serious, 2 patients) Insomnia (below serious, 1 patient) Poor quality sleep (below serious, 1 patient) Tachycardia (below serious, 1 patient) Dissociation (below serious, 1 patient) Dizziness (below serious, 1 patient) Hypertension (below serious, 1 patient) Upper respiratory tract infection (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01920555
2.55 mg/kg single, intravenous (total daily dose) Dose: 2.55 mg/kg Route: intravenous Route: single Dose: 2.55 mg/kg Sources: https://clinicaltrials.gov/ct2/show/NCT01089361	unhealthy n = 10 Health Status: unhealthy Condition: Sepsis Population Size: 10 Sources: https://clinicaltrials.gov/ct2/show/NCT01089361	Other AEs: Pericardial effusion, Ventricular tachycardia... Other AEs: Pericardial effusion (serious, 1 patient) Ventricular tachycardia (serious, 1 patient) Delirium (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01089361

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781	substrate 1037		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512 OCT2 647 OCT3 150	CYP2B6 664	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/	likely	unlikely (co-administration study) Comment: Compared ketamine group with the control group, there were no significant difference for AUC of metroprolol, omeprazole and tolbutamide, it show that the ketamine may not induce or inhibit the activity of CYP1A2, CYP3A4 and CYP2B6 enzyme Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/
CYP2B6 1001	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/	likely	unlikely (co-administration study) Comment: Compared ketamine group with the control group, there were no significant difference for AUC of metroprolol, omeprazole and tolbutamide, it show that the ketamine may not induce or inhibit the activity of CYP1A2, CYP3A4 and CYP2B6 enzyme Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/
CYP3A4 1925	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/	likely	unlikely (co-administration study) Comment: Compared ketamine group with the control group, there were no significant difference for AUC of metroprolol, omeprazole and tolbutamide, it show that the ketamine may not induce or inhibit the activity of CYP1A2, CYP3A4 and CYP2B6 enzyme Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 114.5 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 22.7 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 225.7 uM]

Drug as victim

Target	Modality	Activity
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016812Orig1s046lbl.pdf#page=12 Page: 12.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016812Orig1s046lbl.pdf#page=12 Page: 12.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12095

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6121	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6121
ChemicalBook	CB12463567	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12463567
ChemicalBook	CB32728970	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32728970

PubMed

Title	Date	PubMed
Ketamine-pancuronium-narcotic technic for cardiovascular surgery in infants--a comparative study.	1975 Nov-Dec	1239221
Effects of halothane anesthesia on the biodisposition of ketamine in rats.	1976 Mar	1263110
Emergence delirium following oral ketamine.	1992 Sep	1519802
Determination of absolute configuration of ketamine enantiomers by HPLC-CD-UV technique.	1999	10561702
Cardiovascular pathology possibly associated with ketamine/xylazine anesthesia in Dutch belted rabbits.	1999 Apr	10331545
[Ketamine].	1999 Mar	10228376
Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice.	1999 Mar	10211593
Prolonged analgesic effect of ketamine, an N-methyl-D-aspartate receptor inhibitor, in patients with chronic pain.	1999 May	10215688
Ketamine effects on eye movements.	2000 Dec	11063920
The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans.	2000 Feb	10648330
Ketamine sedation for the reduction of children's fractures in the emergency department.	2000 Jul	10901305
Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.	2000 Oct	11027905
Interindividual differences in the analgesic response to ketamine in chronic orofacial pain.	2001	11558979
NMDA receptor blockade prevents nitroglycerin-induced headaches.	2001 Jul-Aug	11554966
Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism.	2001 Jun	11454027
[Ketamine--dreams and realities].	2002	11974440
Interaction of intravenous anesthetics with recombinant human M1-M3 muscarinic receptors expressed in chinese hamster ovary cells.	2002 Dec	12456425
Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man.	2003 Mar	12680739
The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.	2003 Sep	12911367
Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy.	2004 Oct	15516884
Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with severe cancer pain from metastatic neuroblastoma.	2004 Oct	15454842
Ketamine pretreatment with venous occlusion attenuates pain on injection with propofol.	2005 Jan	15816578
Comparison of ephedrine and ketamine in prevention of injection pain and hypotension due to propofol induction.	2005 Jan	15816573
Characterization of morphine-induced hyperalgesia in male and female rats.	2005 Mar	15733632
Ischemic brain damage after ketamine and xylazine treatment in a young laboratory monkey (Macaca fascicularis).	2005 Sep	16138776

Patents

Sample Use Guides

In Vivo Use Guide

Intravenous Route: The initial dose of Ketalar (ketamine hydrochloride injection) administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). The average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb). Intramuscular Route: The initial dose of Ketalar administered intramuscularly may range from 6.5 to 13 mg/kg (3 to 6 mg/lb). A dose of 10 mg/kg (5 mg/lb) will usually produce 12 to 25 minutes of surgical anesthesia.

Route of Administration: Other

In Vitro Use Guide

Primary cultures of cortical neurons treated with ketamine (10 μM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones

Name

Type

Language

KETAMINE

Official Name

English

NSC-70151

Code

English

PMI-150

Code

English

KETAFOL COMPONENT KETAMINE

Brand Name

English

VETAKET

Brand Name

English

CALYPSOL

Brand Name

English

TEKAM

Brand Name

English

CYCLOHEXANONE, 2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-, (±)-

Systematic Name

English

(±)-2-(O-CHLOROPHENYL)-2-(METHYLAMINO)CYCLOHEXANONE

Common Name

English

(±)-KETAMINE

Common Name

English

IMALGENE 1000

Brand Name

English

KETASOL 100

Brand Name

English

Special K

Common Name

English

ANAKET V

Brand Name

English

KETAMINE [VANDF]

Common Name

English

NARKETAN

Brand Name

English

CYCLOHEXANONE, 2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-

Systematic Name

English

KETAMINE [MI]

Common Name

English

URSOTAMIN

Brand Name

English

Ketamine [WHO-DD]

Common Name

English

CLORKETAM 1000

Brand Name

English

DL-KETAMINE

Common Name

English

ketamine [INN]

Common Name

English

KETAMINE [HSDB]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245