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Record Information
Version2.0
Creation Date2009-07-21 20:27:43 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2900
Identification
Common NamePropofol
ClassSmall Molecule
DescriptionPropofol is an intravenous anaesthetic agent used for induction and maintenance of general anaesthesia. IV administration of propfol is used to induce unconsciousness after which anaesthesia may be maintained using a combination of medications. Recovery from propofol-induced anaesthesia is generally rapid and associated with less frequent side effects (e.g. drowsiness, nausea, vomiting) than with thiopental, methohexital, and etomidate. Propofol may be used prior to diagnostic procedures requiring anaesthesia, in the management of refractory status epilepticus, and for induction and/or maintenance of anaesthesia prior to and during surgeries.
Compound Type
  • Anesthetic, Intravenous
  • Anticonvulsant
  • Antiemetic
  • Drug
  • Free Radical Scavenger
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,6-Bis(1-methylethyl)phenol
2,6-Diisopropylphenol
Anepol
Anespro
Anesvan
Critifol
Diisopropylphenol
Diprivan
Disoprivan
Disoprofol
Dormofol
Fresofol
Gobbifol
Hipnolam
Hypro
IV-Pro
Lipuro
Oleo-Lax
Plofed
Profol
Profolen
Propofabb
Propofil
Propofolum
Propogen
Propolipid
Propovan
Propoven
Provive
Rapinovet
Recofol
Safol
Trivam
Troypofol
Unifol
Chemical FormulaC12H18O
Average Molecular Mass178.271 g/mol
Monoisotopic Mass178.136 g/mol
CAS Registry Number2078-54-8
IUPAC Name2,6-bis(propan-2-yl)phenol
Traditional Namepropofol
SMILESCC(C)C1=CC=CC(C(C)C)=C1O
InChI IdentifierInChI=1S/C12H18O/c1-8(2)10-6-5-7-11(9(3)4)12(10)13/h5-9,13H,1-4H3
InChI KeyInChIKey=OLBCVFGFOZPWHH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cumenes. These are aromatic compounds containing a prop-2-ylbenzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassCumenes
Direct ParentCumenes
Alternative Parents
Substituents
  • Phenylpropane
  • Cumene
  • 1-hydroxy-4-unsubstituted benzenoid
  • Phenol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical Roles
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point18°C
Boiling Point256°C
Solubility124 mg/L
LogP3.79
Predicted Properties
PropertyValueSource
Water Solubility0.16 g/LALOGPS
logP3.81ALOGPS
logP4.16ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)10.98ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity56.42 m³·mol⁻¹ChemAxon
Polarizability21.61 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01t9-4900000000-9238ef924bbbfe181bdcJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0079-8590000000-6ada855df5d0fd97f0b7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-40f0918750264d7e34e2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-3900000000-fa9d883374aeb7d58af5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01ox-9500000000-08cc06244cce31efd090JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-d85c9325119ea81302f8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-d81a7f98827c18689c1dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-1900000000-40cc01d9032f866dffc1JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-03di-2900000000-52d81dde2dccf378a450JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureRapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes. Parenteral (intravenous injection) (12); inhalation (12) ; dermal (12)
Mechanism of ToxicityThe action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.
MetabolismPropofol is rapidly distributed into peripheral tissues after absorption. It is highly protein bound in vivo and is metabolised by conjugation in the liver. Propofol is metabolized mainly by glucuronidation by uridine diphosphate-glucuronosyltransferases (UGTs) and by hydroxylation by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 participate in later steps in propofol metabolism. An unidentified route of extrahepatic metabolism may also exist, suggested by the fact that propofol clearance exceeds estimated hepatic blood flow. (12, 4, 1). Propofol is hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol. Route of Elimination: It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. Half Life: Initial distribution phase t1/2α=1.8-9.5 minutes. Second redistirubtion phase t1/2β=21-70 minutes. Terminal elimination phase t1/2γ=1.5-31 hours.
Toxicity ValuesIV LD50=53 mg/kg (mice), 42 mg/kg (rats). Oral LD50 (as a solution in soybean oil)=1230 mg/kg (mice), 600 mg/kg (rats)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIts widespread use as an anesthetic induction agent has largely replaced that of sodium pentothal. It is also commonly used in veterinary medicine. (12). Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus.
Minimum Risk LevelNot Available
Health EffectsMild myoclonic movements are common, as with other intravenous hypnotic agents. Another recently described rare, but serious, side effect is propofol infusion syndrome. This potentially lethal metabolic derangement has been reported in critically-ill patients after a prolonged infusion of high-dose propofol in combination with catecholamines and/or corticosteroids. Overdose of these agents is likely to cause cardiorespiratory depression. (12, 14) They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsAside from the hypotension (mainly through vasodilatation) and transient apnea following induction doses, one of propofol's most frequent side effects is pain on injection, especially in smaller veins. A more serious but rare side effect is dystonia.
TreatmentIf overdosage occurs, Propofol administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents. (16)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00818
HMDB IDHMDB14956
PubChem Compound ID4943
ChEMBL IDCHEMBL526
ChemSpider ID4774
KEGG IDC07523
UniProt IDNot Available
OMIM ID
ChEBI ID8495
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPropofol
PDB IDPFL
ACToR ID3040
Wikipedia LinkPropofol
References
Synthesis Reference

John R. Carpenter, “Propofol-based anesthetic and method of making same.” U.S. Patent US6150423, issued May, 1977.

MSDSLink
General References
  1. Restrepo JG, Garcia-Martin E, Martinez C, Agundez JA: Polymorphic drug metabolism in anaesthesia. Curr Drug Metab. 2009 Mar;10(3):236-46. [19442086 ]
  2. Vasile B, Rasulo F, Candiani A, Latronico N: The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med. 2003 Sep;29(9):1417-25. Epub 2003 Aug 6. [12904852 ]
  3. Barann M, Urban B, Stamer U, Dorner Z, Bonisch H, Bruss M: Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis. Eur J Pharmacol. 2006 Feb 15;531(1-3):54-8. Epub 2006 Jan 19. [16427041 ]
  4. Gunther S, McMillan PJ, Wallace LJ, Muller S: Plasmodium falciparum possesses organelle-specific alpha-keto acid dehydrogenase complexes and lipoylation pathways. Biochem Soc Trans. 2005 Nov;33(Pt 5):977-80. [16246025 ]
  5. Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL: A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care. 2008 Jan;36(1):74-8. [18326136 ]
  6. Hong JY, Kang YS, Kil HK: Anaesthesia for day case excisional breast biopsy: propofol-remifentanil compared with sevoflurane-nitrous oxide. Eur J Anaesthesiol. 2008 Jun;25(6):460-7. doi: 10.1017/S026502150800375X. Epub 2008 Feb 26. [18298873 ]
  7. Takahashi O, Hiraga K: 4-tert-butyl-2,6-diisopropylphenol: Another phenol inducing hemorrhage in rats. Toxicol Lett. 1980 Feb;5(2):147-50. [7466839 ]
  8. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  9. MICROMEDEX Thomson Health Care (2002). USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. Englewood, CO: MICROMEDEX Thomson Health Care. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc.
  10. Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206
  11. Wikipedia. Barium titanate. Last Updated 27 April 2009. [Link]
  12. Wikipedia. Propofol. Last Updated 9 August 2009. [Link]
  13. Chemicalland21.com (2009). 2,6-Diisopropylphenol (Propofol). [Link]
  14. Wikipedia. Tramadol. Last Updated 8 August 2009. [Link]
  15. Drugs.com [Link]
  16. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Fatty acid amide hydrolase activity
Specific Function:
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates.
Gene Name:
FAAH
Uniprot ID:
O00519
Molecular Weight:
63065.28 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5052 uMNot AvailableBindingDB 50058046
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Lambert DM, Fowler CJ: The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications. J Med Chem. 2005 Aug 11;48(16):5059-87. [16078824 ]
  3. Wikipedia. Propofol. Last Updated 9 August 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Wikipedia. Propofol. Last Updated 9 August 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory98.9 uMNot AvailableBindingDB 50058046
References
  1. Senturk M, Gulcin I, Dastan A, Kufrevioglu OI, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols. Bioorg Med Chem. 2009 Apr 15;17(8):3207-11. doi: 10.1016/j.bmc.2009.01.067. Epub 2009 Feb 4. [19231207 ]
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory19.5 uMNot AvailableBindingDB 50058046
References
  1. Senturk M, Gulcin I, Dastan A, Kufrevioglu OI, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols. Bioorg Med Chem. 2009 Apr 15;17(8):3207-11. doi: 10.1016/j.bmc.2009.01.067. Epub 2009 Feb 4. [19231207 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB2
Uniprot ID:
P47870
Molecular Weight:
59149.895 Da
References
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [16402123 ]
General Function:
Gaba-gated chloride ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
References
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [16402123 ]
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Wikipedia. Propofol. Last Updated 9 August 2009. [Link]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
References
  1. Haeseler G, Karst M, Foadi N, Gudehus S, Roeder A, Hecker H, Dengler R, Leuwer M: High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues. Br J Pharmacol. 2008 Sep;155(2):265-75. doi: 10.1038/bjp.2008.255. Epub 2008 Jun 23. [18574460 ]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Haeseler G, Karst M, Foadi N, Gudehus S, Roeder A, Hecker H, Dengler R, Leuwer M: High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues. Br J Pharmacol. 2008 Sep;155(2):265-75. doi: 10.1038/bjp.2008.255. Epub 2008 Jun 23. [18574460 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.86 uMATG_PXR_TRANSAttagene
AC507.37 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
11. GABA-A receptor (anion channel) (Protein Group)
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88