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 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf	Primary		Approved 8583	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
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
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
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
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
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
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
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
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
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
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
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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 620 OCT2 779 OCT3 159	CYP2B6 776	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 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 1160	inducer 1966 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 2633	inducer 1966 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 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 114.5 uM]
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 22.7 uM]
OCT3 161	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 225.7 uM]

Drug as victim

Target	Modality	Activity
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016812Orig1s046lbl.pdf#page=12 Page: 12.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443184/	yes
CYP3A4 1946	substrate 4014 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 2263	inhibitor 2237 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
Effects of halothane anesthesia on the biodisposition of ketamine in rats.	1976 Mar	1263110
Venodilator effects of adenosine triphosphate and sodium nitroprusside; comparisons during controlled hypotension.	1987 Sep 1	15235850
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
Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy.	1999 Feb	10027033
[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
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.	1999 May	10215643
Ketamine: review of its pharmacology and its use in pediatric anesthesia.	1999 Winter	10551055
Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats.	2000 Aug	10928976
Ketamine effects on eye movements.	2000 Dec	11063920
Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.	2000 Feb	10743446
Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism.	2001 Jun	11454027
Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.	2001 Mar	11240090
In and out of the K-hole: a comparison of the acute and residual effects of ketamine in frequent and infrequent ketamine users.	2001 May	11331033
Ketamine in war/tropical surgery (a final tribute to the racemic mixture).	2002 May	12091028
The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance.	2002 May	11973202
Ketamine as an adjuvant to opioids for cancer pain.	2003	12535471
Schizophrenia, VIII: pharmacologic models.	2003 Dec	14638574
Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity.	2003 Feb	12609230
Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man.	2003 Mar	12680739
Pretreatment with intravenous ketamine reduces propofol injection pain.	2003 Nov	14617116
Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.	2003 Nov	14581915
[Expression of HSP70 induced by ketamine in the hippocampus of rat at different ages].	2004 Jul	15291108
Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen.	2004 Jul	15207038
Influence of O(3)/O(2)-pneumoperitoneum as an oxidative stressor on duration of anaesthesia, loss of different reflexes and cytokine mRNA expression.	2004 Jul	15207037
Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study.	2004 Mar	14727004
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
Participation of adenosine system in the ketamine-induced motor activity in mice.	2005 Jan-Feb	15849377
Ketamine and amphetamine both enhance synaptic transmission in the amygdala-nucleus accumbens pathway but with different time-courses.	2005 Jul	15858833
Severe refractory status epilepticus owing to presumed encephalitis.	2005 Mar	15832606
Characterization of morphine-induced hyperalgesia in male and female rats.	2005 Mar	15733632
Effect of N-methyl-D-aspartate receptor epsilon1 subunit gene disruption of the action of general anesthetic drugs in mice.	2005 Mar	15731593
Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line.	2005 Mar-Apr	15720977
Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review).	2005 Nov	16223384
[Comparison of the suppressive effects of tramadol and low-dose ketamine on the patients with postoperative hyperalgesia after remifentanil-based anaesthesia].	2005 Oct	16285546
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

TEKAM

Preferred Name

English

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

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