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targets (3) enzymes (1)
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Identification
Name Thiamylal
Accession Number DB01154 (APRD00154)
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Surital
Thioseconal
Brand mixtures Not Available
Categories
  • Hypnotics and Sedatives
  • GABA Modulators
  • Anesthetics, Intravenous
CAS number 77-27-0
Weight Average: 254.349
Monoisotopic: 254.10889852
Chemical Formula C12H18N2O2S
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Barbiturates
  • Lactams
Substructures
  • Barbiturates
  • Carbonyl Compounds
  • Alkanes and Alkenes
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Ureas and Derivatives
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Lactams
Pharmacology
Indication Used for the production of complete anaesthesia of short duration, for the induction of general anaesthesia, and for inducing a hypnotic state.
Pharmacodynamics Thiamylal, 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 action Thiamylal 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.
Absorption Rapidly absorbed (high lipid solubility).
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic.
Route of elimination Not Available
Half life Although no studies have been performed on humans, the half-life in cats is 14.3 hours.
Clearance Not Available
Toxicity Intravenous LD50 in rat is 51 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Parkedale pharmaceuticals inc
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 132-133 °C PhysProp
water solubility 49.4 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 3.23 HANSCH,C ET AL. (1995)
logS -3.46 ADME Research, USCD
pKa 7.48 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 5.06e-02 g/l ALOGPS
logP 3.11 ALOGPS
logP 2.92 ChemAxon
logS -3.7 ALOGPS
pKa (strongest acidic) 7.2 ChemAxon
pKa (strongest basic) -3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 58.2 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 70.64 ChemAxon
polarizability 26.75 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D06106 Link_out
KEGG Compound C07846 Link_out
PubChem Compound 3032285 Link_out
PubChem Substance 46506261 Link_out
ChemSpider 2297298 Link_out
ChEBI 9536 Link_out
ChEMBL 9536 Link_out
Therapeutic Targets Database DAP000684 Link_out
PharmGKB PA164746997 Link_out
Drug Product Database 620823 Link_out
Wikipedia http://en.wikipedia.org/wiki/Thiamylal Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

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 rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium (By similarity)

Organism class: human
UniProt ID: Q15842 Link_out
Gene: KCNJ8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

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 rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium

Organism class: human
UniProt ID: Q14654 Link_out
Gene: KCNJ11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19