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Identification
NameThiamylal
Accession NumberDB01154  (APRD00154)
TypeSmall Molecule
GroupsApproved
Description

A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)

Structure
Thumb
Synonyms
SynonymLanguageCode
5-Allyl-5-(1-methylbutyl)-2-thiobarbituric acidNot AvailableNot Available
5-Allyl-5-(1-methylbutyl)-2-thioxodihydro-4,6(1H,5H)-pyrimidinedioneNot AvailableNot Available
5-Allyl-5-(1-methylbutyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dioneNot AvailableNot Available
dihydro-5-(1-Methylbutyl)-5-(2-propenyl)-2-thioxo-4,6(1H,5H)-pyrimidinedioneNot AvailableNot Available
ThiamylalNot AvailableNot Available
ThioseconalNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
SuritalNot Available
ThioseconalNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number77-27-0
WeightAverage: 254.349
Monoisotopic: 254.10889852
Chemical FormulaC12H18N2O2S
InChI KeyXLOMZPUITCYLMJ-UHFFFAOYSA-N
InChI
InChI=1S/C12H18N2O2S/c1-4-6-8(3)12(7-5-2)9(15)13-11(17)14-10(12)16/h5,8H,2,4,6-7H2,1,3H3,(H2,13,14,15,16,17)
IUPAC Name
5-(pentan-2-yl)-5-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
SMILES
CCCC(C)C1(CC=C)C(=O)NC(=S)NC1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentThiobarbituric Acid Derivatives
Alternative parentsDiazinanes; Secondary Carboxylic Acid Amides; Organic Thiocarbonic Acid Derivatives; Polyamines; Carboxylic Acids
Substituents1,3-diazinane; secondary carboxylic acid amide; carboxamide group; thiocarbonic acid derivative; carboxylic acid derivative; polyamine; carboxylic acid; organonitrogen compound
Classification descriptionThis compound belongs to the thiobarbituric acid derivatives. These are organic compounds containing a 2-thioxodihydropyrimidine-4,6(1H,5H)-dione skeleton.
Pharmacology
IndicationUsed for the production of complete anaesthesia of short duration, for the induction of general anaesthesia, and for inducing a hypnotic state.
PharmacodynamicsThiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia.
Mechanism of actionThiamylal 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.
AbsorptionRapidly absorbed (high lipid solubility).
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeAlthough no studies have been performed on humans, the half-life in cats is 14.3 hours.
ClearanceNot Available
ToxicityIntravenous LD50 in rat is 51 mg/kg.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.5532
Blood Brain Barrier + 0.9582
Caco-2 permeable - 0.5361
P-glycoprotein substrate Non-substrate 0.5169
P-glycoprotein inhibitor I Inhibitor 0.5544
P-glycoprotein inhibitor II Non-inhibitor 0.9368
Renal organic cation transporter Non-inhibitor 0.8887
CYP450 2C9 substrate Non-substrate 0.8124
CYP450 2D6 substrate Non-substrate 0.8589
CYP450 3A4 substrate Non-substrate 0.7011
CYP450 1A2 substrate Non-inhibitor 0.7869
CYP450 2C9 substrate Non-inhibitor 0.5555
CYP450 2D6 substrate Non-inhibitor 0.9131
CYP450 2C19 substrate Non-inhibitor 0.6101
CYP450 3A4 substrate Non-inhibitor 0.8138
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8282
Ames test Non AMES toxic 0.6521
Carcinogenicity Non-carcinogens 0.9047
Biodegradation Not ready biodegradable 0.9974
Rat acute toxicity 2.7058 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9781
hERG inhibition (predictor II) Non-inhibitor 0.8205
Pharmacoeconomics
Manufacturers
  • Parkedale pharmaceuticals inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point132-133 °CPhysProp
water solubility49.4 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.23HANSCH,C ET AL. (1995)
logS-3.46ADME Research, USCD
pKa7.48SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0506ALOGPS
logP3.11ALOGPS
logP2.92ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)7.2ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity70.64 m3·mol-1ChemAxon
Polarizability26.75 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD06106
KEGG CompoundC07846
PubChem Compound3032285
PubChem Substance46506261
ChemSpider2297298
ChEBI9536
ChEMBLCHEMBL440
Therapeutic Targets DatabaseDAP000684
PharmGKBPA164746997
Drug Product Database620823
WikipediaThiamylal
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

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. Pubmed
  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. Pubmed
  3. Sugimura M, Kitayama S, Morita K, Imai Y, Irifune M, Takarada T, Kawahara M, Dohi T: Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice. Pharmacol Biochem Behav. 2002 May;72(1-2):111-6. Pubmed
  4. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. Pubmed
  5. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  6. 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. Pubmed
  7. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed
  8. Grasshoff C, Netzhammer N, Schweizer J, Antkowiak B, Hentschke H: Depression of spinal network activity by thiopental: shift from phasic to tonic GABA receptor-mediated inhibition. Neuropharmacology. 2008 Oct;55(5):793-802. Epub 2008 Jun 21. Pubmed

2. ATP-sensitive inward rectifier potassium channel 8

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 8 Q15842 Details

References:

  1. Eguchi S, Kawano T, Oshita S, Nakajo N: [Effects of propofol and thiamylal on nicorandil induced ATP-sensitive potassium channel activities in cultured rat aortic smooth muscle cells] Masui. 2005 Apr;54(4):364-9. Pubmed
  2. Kawano T, Oshita S, Takahashi A, Tsutsumi Y, Tomiyama Y, Kitahata H, Kuroda Y, Nakaya Y: Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels. Anesthesiology. 2004 Feb;100(2):338-46. Pubmed
  3. Tsutsumi Y, Oshita S, Kitahata H, Kuroda Y, Kawano T, Nakaya Y: Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes. Anesthesiology. 2000 Apr;92(4):1154-9. Pubmed

3. ATP-sensitive inward rectifier potassium channel 11

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 11 Q14654 Details

References:

  1. Kawano T, Oshita S, Takahashi A, Tsutsumi Y, Tomiyama Y, Kitahata H, Kuroda Y, Nakaya Y: Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels. Anesthesiology. 2004 Feb;100(2):338-46. Pubmed
  2. Tsutsumi Y, Oshita S, Kitahata H, Kuroda Y, Kawano T, Nakaya Y: Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes. Anesthesiology. 2000 Apr;92(4):1154-9. Pubmed
  3. Eguchi S, Kawano T, Oshita S, Nakajo N: [Effects of propofol and thiamylal on nicorandil induced ATP-sensitive potassium channel activities in cultured rat aortic smooth muscle cells] Masui. 2005 Apr;54(4):364-9. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Sueyasu M, Fujito K, Shuto H, Mizokoshi T, Kataoka Y, Oishi R: Protein binding and the metabolism of thiamylal enantiomers in vitro. Anesth Analg. 2000 Sep;91(3):736-40. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13