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Identification
NameThiamylal
Accession NumberDB01154  (APRD00154)
TypeSmall Molecule
GroupsApproved, Vet Approved
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
5-Allyl-5-(1-methylbutyl)-2-thiobarbituric acid
5-Allyl-5-(1-methylbutyl)-2-thioxodihydro-4,6(1H,5H)-pyrimidinedione
5-Allyl-5-(1-methylbutyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
dihydro-5-(1-Methylbutyl)-5-(2-propenyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione
Thiamylal
Thioseconal
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
SuritalNot Available
ThioseconalNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Thiamylal sodium
ThumbNot applicableDBSALT001404
Categories
UNII01T23W89FR
CAS number77-27-0
WeightAverage: 254.349
Monoisotopic: 254.10889852
Chemical FormulaC12H18N2O2S
InChI KeyInChIKey=XLOMZPUITCYLMJ-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
Taxonomy
DescriptionThis compound 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
  • Thiocarbonic acid derivative
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.5532
Blood Brain Barrier+0.9582
Caco-2 permeable-0.5361
P-glycoprotein substrateNon-substrate0.5169
P-glycoprotein inhibitor IInhibitor0.5544
P-glycoprotein inhibitor IINon-inhibitor0.9368
Renal organic cation transporterNon-inhibitor0.8887
CYP450 2C9 substrateNon-substrate0.8124
CYP450 2D6 substrateNon-substrate0.8589
CYP450 3A4 substrateNon-substrate0.7011
CYP450 1A2 substrateNon-inhibitor0.7869
CYP450 2C9 inhibitorNon-inhibitor0.5555
CYP450 2D6 inhibitorNon-inhibitor0.9131
CYP450 2C19 inhibitorNon-inhibitor0.6101
CYP450 3A4 inhibitorNon-inhibitor0.8138
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8282
Ames testNon AMES toxic0.6521
CarcinogenicityNon-carcinogens0.9047
BiodegradationNot ready biodegradable0.9974
Rat acute toxicity2.7058 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9781
hERG inhibition (predictor II)Non-inhibitor0.8205
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
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 Solubility0.0506 mg/mLALOGPS
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 si...
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. [PubMed: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. [PubMed:17016423 ]
  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:11900777 ]
  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:14579514 ]
  5. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [PubMed:10209232 ]
  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:11264449 ]
  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:10487207 ]
  8. Grasshoff C, Netzhammer N, Schweizer J, Antkowiak B, Hentschke H: Depression of spinal network activity by thiopental: shift from phasic to tonic GABA(A) receptor-mediated inhibition. Neuropharmacology. 2008 Oct;55(5):793-802. doi: 10.1016/j.neuropharm.2008.06.026. Epub 2008 Jun 21. [PubMed:18619475 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Inward rectifier potassium channel activity
Specific Function:
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward...
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular Weight:
47967.455 Da
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:15852621 ]
  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:14739809 ]
  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:10754636 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Voltage-gated potassium channel activity
Specific Function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectific...
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular Weight:
43540.375 Da
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:14739809 ]
  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:10754636 ]
  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:15852621 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
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:10960410 ]
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Drug created on June 13, 2005 07:24 / Updated on November 30, 2015 12:10