Thiopental

Overview

Description
A medication used for anesthesia and to reduce pressure in the head during brain surgery.
Description
A medication used for anesthesia and to reduce pressure in the head during brain surgery.
DrugBank ID
DB00599
Type
Small Molecule
US Approved
NO
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
2
Phase 2
3
Phase 3
3
Phase 4
5
Therapeutic Categories
  • Anticonvulsants
  • Barbiturates

Identification

Summary

Thiopental is a barbiturate used to induce general anesthesia, treat convulsions, and reduce intracranial pressure.

Generic Name
Thiopental
DrugBank Accession Number
DB00599
Background

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)

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Weight
Average: 242.338
Monoisotopic: 242.10889852
Chemical Formula
C11H18N2O2S
Synonyms
  • (±)-thiopental
  • 2-Thio-5-ethyl-5-sec-pentylbarbituric acid
  • 5-Ethyl-5-(1-methyl-butyl)-2-thioxo-dihydro-pyrimidine-4,6-dione
  • Penthiobarbital
  • Pentothiobarbital
  • Thiopental
  • Thiopentobarbital
  • Thiopentobarbitone
  • Thiopentobarbituric acid
  • Thiopentone
  • Tiopentale

Pharmacology

Indication

For 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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofSeizures•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Mechanism of action

Thiopental 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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-2
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-3
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-4
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-5
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-6
potentiator
Humans
UNeuronal acetylcholine receptor subunit alpha-4
antagonist
Humans
UNeuronal acetylcholine receptor subunit alpha-7
antagonist
Humans
UGlutamate receptor 2
antagonist
Humans
UGlutamate receptor ionotropic, kainate 2
antagonist
Humans
UFatty-acid amide hydrolase 1
inhibitor
Humans
UMuscarinic acetylcholine receptor M3Not AvailableHumans
Absorption

Rapidly absorbed.

Volume of distribution

Not Available

Protein binding

Approximately 80% of the drug in the blood is bound to plasma protein.

Metabolism

Thiopental is extensively metabolized, primarily in the liver, resulting in only 0.3% of an administered dose being excreted unchanged in the urine.7 Ring desulfuration leads to the generation of an active metabolite, pentobarbital, that exists in concentrations approximately 3-10% that of the parent concentration.5 Thiopental and pentobarbital are also subject to both oxidation and hydroxylation to carboxylic acids and alcohols, respectively, all of which are pharmacologically inert.5

While many of the specifics regarding thiopental biotransformation have not been elucidated, including the enzymes responsible, the oxidation of thiopental to its carboxylic acid may be the major driver of thiopental detoxification as this product appears to account for 10-25% of renally excreted drug.5

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Route of elimination

Not Available

Half-life

3-8 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Overdosage may occur from 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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Thiopental is combined with 1,2-Benzodiazepine.
AbaloparatideThiopental may increase the hypotensive activities of Abaloparatide.
AbataceptThe metabolism of Thiopental can be increased when combined with Abatacept.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Thiopental.
AcebutololThiopental may increase the hypotensive activities of Acebutolol.
Food Interactions
  • Avoid alcohol. Additive CNS depression may occur if alcohol is consumed with thiopental.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Thiopental sodium49Y44QZL7071-73-8AWLILQARPMWUHA-UHFFFAOYSA-M
International/Other Brands
Anestho (Incepta) / Bensulf (Fada ) / Bitol Sodium (Brookes) / Ekipental (Tüm Ekip) / Farmotal (Marvecs Pharma Services) / Intraval Sodium (Abbott) / Pental Sodyum (I.E. Ulagay) / Pentazol (Swiss Parenterals) / Penthal (Oboi) / Penthotal Sodium (Abbott) / Pentotan (Choong Wae) / Pentotex (Rotexmedica) / Pentothal (Hospira) / Ravonal (Ravonal) / Thiopen (ACI) / Tiopental (Richmond) / Trapanal (Nycomed)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Thiopental SodiumInjection, powder, for solution50 mg/1mLIntravenousHospira, Inc.2010-05-252011-01-21US flag
Thiopental SodiumInjection, powder, for solution25 mg/1mLIntravenousHospira, Inc.2010-05-252011-01-21US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Thiopental SodiumThiopental sodium (50 mg/1mL)Injection, powder, for solutionIntravenousHospira, Inc.2010-05-252011-01-21US flag
Thiopental SodiumThiopental sodium (25 mg/1mL)Injection, powder, for solutionIntravenousHospira, Inc.2010-05-252011-01-21US flag

Categories

ATC Codes
N01AF03 — ThiopentalN05CB01 — Combinations of barbituratesN05CA19 — Thiopental
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Thiobarbituric acid derivatives
Alternative Parents
Diazinanes / Thioureas / Carboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
1,3-diazinane / Aliphatic heteromonocyclic compound / Azacycle / Carbonyl group / Carboxylic acid derivative / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
barbiturates (CHEBI:102166)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
JI8Z5M7NA3
CAS number
76-75-5
InChI Key
IUJDSEJGGMCXSG-UHFFFAOYSA-N
InChI
InChI=1S/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)
IUPAC Name
5-ethyl-5-(pentan-2-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
SMILES
CCCC(C)C1(CC)C(=O)NC(=S)NC1=O

References

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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. Carroll FI, Smith D, Mark LC, Brand L, Perel JM: Determination of optically active thiopental, thiamylal, and their metabolites in human urine. Drug Metab Dispos. 1977 Jul-Aug;5(4):343-54. [Article]
  5. Russo H, Bressolle F: Pharmacodynamics and pharmacokinetics of thiopental. Clin Pharmacokinet. 1998 Aug;35(2):95-134. doi: 10.2165/00003088-199835020-00002. [Article]
  6. Suddock JT, Cain MD: Barbiturate Toxicity . [Article]
  7. EMC Summary of Product Characteristics: Thiopental powder for solution for injection [Link]
Human Metabolome Database
HMDB0014737
KEGG Compound
C07521
PubChem Compound
3000715
PubChem Substance
46504621
ChemSpider
2272258
BindingDB
50058058
RxNav
10493
ChEBI
102166
ChEMBL
CHEMBL441
Therapeutic Targets Database
DAP000661
PharmGKB
PA451664
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sodium_thiopental

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableCesarean Sections / Maternal Hypotension / Preoperative Anxiety / Sedation / Spinal Anesthesia therapy1somestatusstop reasonjust information to hide
Not AvailableCompletedBasic ScienceObesity1somestatusstop reasonjust information to hide
Not AvailableCompletedBasic SciencePhobic Disorders1somestatusstop reasonjust information to hide
Not AvailableCompletedHealth Services ResearchAlcohol Dependency1somestatusstop reasonjust information to hide
Not AvailableCompletedOtherEffect of Drugs1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Abbott laboratories hosp products div
Packagers
  • Baxter International Inc.
  • Hospira Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous1000 mg/1vial
Powder1000 mg/1vial
Powder, for solutionIntravenous
Injection, powder, for solutionIntravenous1 g
Injection
Powder, for solutionIntravenous25 mg / mL
Powder, for solutionIntravenous500 mg
Powder, for solutionIntravenous250 mg / syr
Injection, powder, for solutionIntravenous
Powder, for solutionIntravenous1 g / vial
Powder, for solutionIntravenous5 g / bottle
Injection, powder, for solutionParenteral1 g
Injection, powder, for solution0.5 g
Injection, powder, for solution1 g
Injection, powder, for solutionIntravenous25 mg/1mL
Injection, powder, for solutionIntravenous50 mg/1mL
Injection, powder, for solutionIntravenous0.5 g
Injection, solutionIntravenous0.5 g
Injection, solutionIntravenous1 g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.85HANSCH,C ET AL. (1995)
logS-3.36ADME Research, USCD
pKa7.55SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0398 mg/mLALOGPS
logP3.05ALOGPS
logP2.78Chemaxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.2Chemaxon
pKa (Strongest Basic)-8Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area58.2 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity65.99 m3·mol-1Chemaxon
Polarizability25.7 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.5106
Blood Brain Barrier+0.9505
Caco-2 permeable-0.5463
P-glycoprotein substrateNon-substrate0.5623
P-glycoprotein inhibitor INon-inhibitor0.5373
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.9031
CYP450 2C9 substrateNon-substrate0.8052
CYP450 2D6 substrateNon-substrate0.858
CYP450 3A4 substrateNon-substrate0.6688
CYP450 1A2 substrateNon-inhibitor0.8297
CYP450 2C9 inhibitorNon-inhibitor0.5588
CYP450 2D6 inhibitorNon-inhibitor0.914
CYP450 2C19 inhibitorNon-inhibitor0.5927
CYP450 3A4 inhibitorNon-inhibitor0.8813
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8482
Ames testNon AMES toxic0.6907
CarcinogenicityNon-carcinogens0.8992
BiodegradationNot ready biodegradable0.9917
Rat acute toxicity2.7671 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9827
hERG inhibition (predictor II)Non-inhibitor0.6314
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.6 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00bc-9240000000-1417d556dd6b075ba8eb
Mass Spectrum (Electron Ionization)MSsplash10-0596-9600000000-1b2c7562818b87a3dce1
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-2256e1984e122af286e5
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0090000000-c8a2b96397abdac51af0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-4090000000-3397f51adf5ac5e26757
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9010000000-2049e423160775847315
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-e858eafc5134f3cf550e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-aed0d4351672086bb8bf
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-aed0d4351672086bb8bf
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0090000000-0da49458314b6213fc56
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-4090000000-5e98b0adc2fa68ac83f3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-35496d92c575e3289c20
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-aed0d4351672086bb8bf
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-e858eafc5134f3cf550e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-e858eafc5134f3cf550e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-2f4595765496ded39eec
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0690000000-fd05a332691d8a6d60b7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-1900000000-ed472a09caeab6e79b7a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-01r6-0390000000-2adae763cf0d681466eb
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0900000000-913963ea32dd131b3307
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-b72b71b16561df8c00d3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-9200000000-95192dd6ef20d9ebd7d1
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-160.4264184
predicted
DarkChem Lite v0.1.0
[M-H]-152.52089
predicted
DeepCCS 1.0 (2019)
[M+H]+161.8390184
predicted
DarkChem Lite v0.1.0
[M+H]+156.02324
predicted
DeepCCS 1.0 (2019)
[M+Na]+161.1845184
predicted
DarkChem Lite v0.1.0
[M+Na]+164.6064
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)
Specific Function
GABA-A receptor activity
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. [Article]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
  3. 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. [Article]
  4. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
  5. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:29961870, PubMed:31032849). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:10449790). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). The alpha-2 subunit exhibits synaptogenic activity together with beta-2 and very little to no activity together with beta-3, the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (By similarity)
Specific Function
benzodiazepine receptor activity
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
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. [Article]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:16412217, PubMed:29053855). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:16412217, PubMed:29053855). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (PubMed:16412217, PubMed:29053855)
Specific Function
benzodiazepine receptor activity
Gene Name
GABRA3
Uniprot ID
P34903
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-3
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. [Article]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020)
Specific Function
benzodiazepine receptor activity
Gene Name
GABRA4
Uniprot ID
P48169
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-4
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:14993607, PubMed:29961870, PubMed:30140029, PubMed:31056671). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:30140029). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:30140029). GABAARs containing alpha-5/GABRA5 subunits are mainly extrasynaptic and contribute to the tonic GABAergic inhibition in the hippocampus (By similarity). Extrasynaptic alpha-5-containing GABAARs in CA1 pyramidal neurons play a role in learning and memory processes (By similarity)
Specific Function
GABA receptor binding
Gene Name
GABRA5
Uniprot ID
P31644
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-5
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. [Article]
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:8632757). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). Alpha-6/GABRA6 subunits are found at both synaptic and extrasynaptic sites (PubMed:8632757). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). Extrasynaptic alpha-6-containing receptors contribute to the tonic GABAergic inhibition. Alpha-6 subunits are also present on glutamatergic synapses (By similarity)
Specific Function
benzodiazepine receptor activity
Gene Name
GABRA6
Uniprot ID
Q16445
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-6
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General 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
Specific Function
acetylcholine binding
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
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. [Article]
  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. [Article]
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General 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
Specific Function
acetylcholine binding
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
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. [Article]
  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. [Article]
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:20614889, PubMed:31300657, PubMed:8003671). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (PubMed:14687553). 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 upon entry of monovalent and divalent cations such as sodium and calcium (PubMed:20614889, PubMed:8003671). The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). 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 L-glutamate (By similarity). Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity)
Specific Function
AMPA glutamate receptor activity
Gene Name
GRIA2
Uniprot ID
P42262
Uniprot Name
Glutamate receptor 2
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. [Article]
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Ionotropic glutamate receptor that functions as a cation permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. 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 (PubMed:14511640, PubMed:28180184, PubMed:34375587, PubMed:7536611, PubMed:8730589). Modulates cell surface expression of NETO2. In association with GRIK3, involved in presynaptic facilitation of glutamate release at hippocampal mossy fiber synapses (By similarity)
Specific Function
extracellularly glutamate-gated ion channel activity
Gene Name
GRIK2
Uniprot ID
Q13002
Uniprot Name
Glutamate receptor ionotropic, kainate 2
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. [Article]
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regulating the signaling functions of these molecules (PubMed:17015445, PubMed:19926788, PubMed:9122178). Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (PubMed:17015445, PubMed:9122178). It can also catalyze the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol) (PubMed:21049984). FAAH cooperates with PM20D1 in the hydrolysis of amino acid-conjugated fatty acids such as N-fatty acyl glycine and N-fatty acyl-L-serine, thereby acting as a physiological regulator of specific subsets of intracellular, but not of extracellular, N-fatty acyl amino acids (By similarity)
Specific Function
acylglycerol lipase activity
Gene Name
FAAH
Uniprot ID
O00519
Uniprot Name
Fatty-acid amide hydrolase 1
Molecular Weight
63065.28 Da
References
  1. Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom K, Campbell WB, Hillard CJ: The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol. 2003 Jul;139(5):1005-13. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General 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
Specific Function
acetylcholine binding
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
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. [Article]

Enzymes

Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity

Components:
References
  1. Hoebel BG, Steyrer E, Graier WF: Origin and function of epoxyeicosatrienoic acids in vascular endothelial cells: more than just endothelium-derived hyperpolarizing factor? Clin Exp Pharmacol Physiol. 1998 Oct;25(10):826-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Lerman J. (2014). Neonatal Anesthesia. Springer.

Drug created at June 13, 2005 13:24 / Updated at November 09, 2024 05:56