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Record Information
Version2.0
Creation Date2009-07-21 20:27:14 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2835
Identification
Common NameThiopental
ClassSmall Molecule
DescriptionThiopental is a barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration. It is also used for hypnosis and for the control of convulsive states. It has been used in neurosurgical patients to reduce increased intracranial pressure. It does not produce any excitation but has poor analgesic and muscle relaxant properties. Small doses have been shown to be anti-analgesic and lower the pain threshold. (From Martindale, The Extra Pharmacopoeia, 30th ed, p920)
Compound Type
  • Amide
  • Amine
  • Anesthetic, Intravenous
  • Anticonvulsant
  • Drug
  • GABA Modulator
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-Thiopental
2-Thio-5-ethyl-5-sec-pentylbarbituric acid
5-Ethyl-5-(1-methyl-butyl)-2-thioxo-dihydro-pyrimidine-4,6-dione
Anestho
Bensulf
Bitaryl
Bitol Sodium
Ekipental
Farmotal
Intraval Sodium
Omexolon
Pental Sodyum
Pentazol
Penthal
Penthiobarbital
Penthotal Sodium
Pentotan
Pentotex
Pentothal
Pentothiobarbital
Ravonal
Sodium Pentothal
Thiomebumal
Thiomebumalum
Thionembutal
Thiopen
Thiopentobarbital
Thiopentobarbitone
Thiopentobarbituric acid
Thiopentone
Tiopental
Tiopentale
Trapanal
Chemical FormulaC11H18N2O2S
Average Molecular Mass242.338 g/mol
Monoisotopic Mass242.109 g/mol
CAS Registry Number76-75-5
IUPAC Name5-ethyl-5-(pentan-2-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
Traditional Namethiopental
SMILESCCCC(C)C1(CC)C(O)=NC(=S)N=C1O
InChI IdentifierInChI=1/C11H18N2O2S/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16)
InChI KeyInChIKey=IUJDSEJGGMCXSG-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as thiobarbituric acid derivatives. These are organic compounds containing a 2-thioxodihydropyrimidine-4,6(1H,5H)-dione skeleton.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentThiobarbituric acid derivatives
Alternative Parents
Substituents
  • Thiobarbiturate
  • 1,3-diazinane
  • Thiourea
  • Azacycle
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility3.98e-02 g/L
LogP2.85
Predicted Properties
PropertyValueSource
Water Solubility0.04 g/LALOGPS
logP3.05ALOGPS
logP2.78ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.2ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity65.99 m³·mol⁻¹ChemAxon
Polarizability25.7 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, Positivesplash10-00bc-9240000000-1417d556dd6b075ba8ebJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0900000000-2256e1984e122af286e5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0090000000-c8a2b96397abdac51af0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-4090000000-3397f51adf5ac5e26757JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9010000000-2049e423160775847315JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-e858eafc5134f3cf550eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-aed0d4351672086bb8bfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-aed0d4351672086bb8bfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0090000000-0da49458314b6213fc56JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-4090000000-5e98b0adc2fa68ac83f3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-35496d92c575e3289c20JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-aed0d4351672086bb8bfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-e858eafc5134f3cf550eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-9000000000-e858eafc5134f3cf550eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0900000000-2f4595765496ded39eecJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-1290000000-56a5ebd429075bcf94edJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01ox-1960000000-7b820ca9f1a89eb04af1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01bc-9100000000-fd47f0d49141ce724db7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-3980000000-015294919b010d958051JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-5046a8c65e5598a59005JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9200000000-b61e997b758e9e8e7bdeJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0596-9600000000-1b2c7562818b87a3dce1JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureParenteral (intravenous). Rapidly absorbed.
Mechanism of ToxicityThiopental binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.
MetabolismPrimarily hepatic. Biotransformation products of thiopental are pharmacologically inactive and mostly excreted in the urine. Half Life: 3-8 hours
Toxicity ValuesLD50: 50.6 mg kg −1(95% CI, 50.0–54.9) (i.v, mice) (5)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as the sole anesthetic agent for brief (15 minute) procedures, for induction of anesthesia prior to administration of other anesthetic agents, to supplement regional anesthesia, to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, for the control of convulsive states during or following inhalation anesthesia or local anesthesia, in neurosurgical patients with increased intracranial pressure, and for narcoanalysis and narcosynthesis in psychiatric disorders. Used commonly in the induction phase of general anesthesia. (Sodium-)thiopental is a depressant and is sometimes used during interrogations - not to cause pain (in fact, it may have just the opposite effect), but to weaken the resolve of the subject and make him or her more compliant to pressure. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsThey 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.
SymptomsOverdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. Lethal blood levels may be as low as 1 mg/100 mL for short-acting barbiturates; less if other depressant drugs or alcohol are also present.
TreatmentIt is generally agreed that respiratory depression or arrest due to unusual sensitivity to thiopental sodium or overdosage is easily managed if there is no concomitant respiratory obstruction. If the airway is patent, any method of ventilating the lungs (that prevents hypoxia) should be successful in maintaining other vital functions. Since depression of respiratory activity is one of the characteristic actions of the drug, it is important to observe respiration closely. Should laryngeal spasm occur, it may be relieved by one of the usual methods, such as the use of a relaxant drug or positive pressure oxygen. Endotracheal intubation may be indicated in difficult cases. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00599
HMDB IDHMDB14737
PubChem Compound ID3000715
ChEMBL IDCHEMBL441
ChemSpider ID2272258
KEGG IDC07521
UniProt IDNot Available
OMIM ID
ChEBI ID102166
BioCyc IDNot Available
CTD IDNot Available
Stitch IDThiopental
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkThiopental
References
Synthesis ReferenceNot Available
MSDST3D2835.pdf
General References
  1. Morgan DJ, Blackman GL, Paull JD, Wolf LJ: Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section. Anesthesiology. 1981 Jun;54(6):474-80. [7235275 ]
  2. Perez-Barcena J, Barcelo B, Homar J, Abadal JM, Molina FJ, de la Pena A, Sahuquillo J, Ibanez J: [Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients]. Neurocirugia (Astur). 2005 Feb;16(1):5-12; discussion 12-3. [15756405 ]
  3. WINTERS WD, SPECTOR E, WALLACH DP, SHIDEMAN FE: Metabolism of thiopental-S35 and thiopental-2-C14 by a rat liver mince and identification of pentobarbital as a major metabolite. J Pharmacol Exp Ther. 1955 Jul;114(3):343-57. [13243246 ]
  4. Bory C, Chantin C, Boulieu R, Cotte J, Berthier JC, Fraisse D, Bobenrieth MJ: [Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry]. C R Acad Sci III. 1986;303(1):7-12. [3093002 ]
  5. Ben-Shlomo I, Rosenbaum A, Hadash O, Katz Y: Intravenous midazolam significantly enhances the lethal effect of thiopental but not that of ketamine in mice. Pharmacol Res. 2001 Dec;44(6):509-12. [11735358 ]
  6. Drugs.com [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Ligand-gated ion channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
Gene Name:
CHRNA4
Uniprot ID:
P43681
Molecular Weight:
69956.47 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. [16248797 ]
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [10487207 ]
General Function:
Toxic substance binding
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
Gene Name:
CHRNA7
Uniprot ID:
P36544
Molecular Weight:
56448.925 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. [16248797 ]
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [10487207 ]
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 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [10209232 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [10209232 ]
General Function:
Transporter activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular Weight:
52145.645 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [10209232 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
References
  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [10209232 ]
  2. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA2
Uniprot ID:
P42262
Molecular Weight:
98820.32 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [10487207 ]
General Function:
Kainate selective glutamate receptor activity
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity).
Gene Name:
GRIK2
Uniprot ID:
Q13002
Molecular Weight:
102582.475 Da
References
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. [11264449 ]
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [10487207 ]
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
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA4
Uniprot ID:
P48169
Molecular Weight:
61622.645 Da
References
  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [10209232 ]
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. Hirota K, Hashimoto Y, Lambert DG: Interaction of intravenous anesthetics with recombinant human M1-M3 muscarinic receptors expressed in chinese hamster ovary cells. Anesth Analg. 2002 Dec;95(6):1607-10, table of contents. [12456425 ]