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Identification
Name Ketamine
Accession Number DB01221 (APRD00493)
Type small molecule
Groups approved
Description

A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, N-methyl-D-aspartate) and may interact with sigma receptors. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(-)-Ketamine
(S)-(-)-Ketamine
(S)-Ketamine
CI 581 base
Ketamine Base
Ketamine HCL
l-Ketamine
Salts Not Available
Brand names
Name Company
CLSTA 20
Esketamine
Ketaject
Ketalar
Ketalar base
Ketanest
Ketolar
Brand mixtures Not Available
Categories
  • Analgesics
  • General Anesthetics
  • Excitatory Amino Acid Antagonists
  • Anesthetics, Dissociative
CAS number 6740-88-1
Weight Average: 237.725
Monoisotopic: 237.092041846
Chemical Formula C13H16ClNO
InChI Key InChIKey=YQEZLKZALYSWHR-UHFFFAOYSA-N
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
Plain Text
IUPAC Name
2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one
SMILES
CNC1(CCCCC1=O)C1=CC=CC=C1Cl
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
Substructures
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aromatic compounds
  • Ketones
Pharmacology
Indication For use as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation.
Pharmacodynamics Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. Ketamine is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. The anesthetic state produced by Ketamine has been termed “dissociative anesthesia” in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticularactivating and limbic systems).
Mechanism of action Ketamine has several clinically useful properties, including analgesia and less cardiorespiratory depressant effects than other anaesthetic agents, it also causes some stimulation of the cardiocascular system. Ketamine has been reported to produce general as well as local anaesthesia. It interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.
Absorption Rapidly absorbed following parenteral administration.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic.
Route of elimination Not Available
Half life 2.5-3 hours.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Jhp pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Hospira inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Ketamine hcl powder 7.22 USD g
Ketamine hcl-ns 50 mg/5 ml syr 2.82 USD ml
Ketamine 100 mg/ml vial 2.36 USD ml
Ketalar 100 mg/ml vial 1.95 USD ml
Ketamine hcl-ns 100 mg/10 ml 1.95 USD ml
Ketamine HCl 50 mg/ml Solution 1.77 USD ml
Ketalar 10 mg/ml vial 0.99 USD ml
Ketamine 10 mg/ml vial 0.99 USD ml
Ketalar 50 mg/ml vial 0.75 USD ml
Ketamine 50 mg/ml vial 0.61 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 92.5 °C PhysProp
logP 2.9 Not Available
Predicted Properties
Property Value Source
water solubility 4.64e-02 g/l ALOGPS
logP 2.69 ALOGPS
logP 3.35 ChemAxon
logS -3.7 ALOGPS
pKa (strongest acidic) 18.78 ChemAxon
pKa (strongest basic) 7.45 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 29.1 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 65.55 ChemAxon
polarizability 24.97 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Harrison NL, Simmonds MA: Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381-91. Pubmed
  2. Bergman SA: Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog. 1999 Winter;46(1):10-20. Pubmed
  3. Bonanno FG: Ketamine in war/tropical surgery (a final tribute to the racemic mixture). Injury. 2002 May;33(4):323-7. Pubmed
  4. Lankenau SE, Sanders B, Bloom JJ, Hathazi D, Alarcon E, Tortu S, Clatts MC: First injection of ketamine among young injection drug users (IDUs) in three U.S. cities. Drug Alcohol Depend. 2007 Mar 16;87(2-3):183-93. Epub 2006 Sep 18. Pubmed
  5. Reboso Morales JA, Gonzalez Miranda F: [Ketamine] Rev Esp Anestesiol Reanim. 1999 Mar;46(3):111-22. Pubmed
External Links
Resource Link
KEGG Compound C07525 Link_out
PubChem Compound 3821 Link_out
PubChem Substance 46508295 Link_out
ChemSpider 3689 Link_out
BindingDB 50044140 Link_out
ChEBI 6121 Link_out
ChEMBL 6121 Link_out
Therapeutic Targets Database DAP001148 Link_out
PharmGKB PA450144 Link_out
Drug Product Database 2246796 Link_out
RxList http://www.rxlist.com/cgi/generic3/ketamine.htm Link_out
Drugs.com http://www.drugs.com/cdi/ketamine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ketamine Link_out
ATC Codes
  • N01AX03
  • N01AX14
AHFS Codes
  • 28:04.00
  • 28:04.92
PDB Entries Not Available
FDA label Not Available
MSDS show (67.5 KB)
Interactions
Drug Interactions
Drug Interaction
Memantine Increased risk of CNS adverse effects with this association
Telithromycin Telithromycin may reduce clearance of Ketamine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Ketamine if Telithromycin is initiated, discontinued or dose changed.
Thiotepa Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Ketamine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Ketamine if Thiotepa is initiated, discontinued or dose changed.
Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Ketamine. Consider alternate therapy or monitor for changes in Ketamine therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ketamine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of ketamine if voriconazole is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. Glutamate [NMDA] receptor subunit 3A

Pharmacological action: yes
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism

Organism class: human
UniProt ID: Q8TCU5 Link_out
Gene: GRIN3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. Pubmed
  2. Harrison NL, Simmonds MA: Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381-91. Pubmed
  3. Sinner B, Graf BM: Ketamine. Handb Exp Pharmacol. 2008;(182):313-33. Pubmed
  4. Radovanovic D, Pjevic M: [Ketamine: the past 30 years and its future] Med Pregl. 2003 Sep-Oct;56(9-10):439-45. Pubmed

2. Substance-P receptor

Pharmacological action: unknown
Actions: antagonist

This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is:substance P > substance K > neuromedin K

Organism class: human
UniProt ID: P25103 Link_out
Gene: TACR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Okamoto T, Minami K, Uezono Y, Ogata J, Shiraishi M, Shigematsu A, Ueta Y: The inhibitory effects of ketamine and pentobarbital on substance p receptors expressed in Xenopus oocytes. Anesth Analg. 2003 Jul;97(1):104-10, table of contents. Pubmed

3. D(2) dopamine receptor

Pharmacological action: unknown
Actions: agonist, partial agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Seeman P, Guan HC, Hirbec H: Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse. 2009 Aug;63(8):698-704. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2B6

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Prostaglandin G/H synthase 1

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

5. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20