Identification

Name
Enflurane
Accession Number
DB00228
Description

Enflurane is a halogenated inhalational anesthetic initially approved by the FDA in 1972. Since this date, it has been withdrawn from the US market.18,19 Unlike its other inhalational anesthetic counterparts including isoflurane and halothane, enflurane is known to induce seizure activity. In addition, it is known to cause increased cardio depressant effects when compared to other inhaled anesthetics.5

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure
Thumb
Weight
Average: 184.492
Monoisotopic: 183.971433418
Chemical Formula
C3H2ClF5O
Synonyms
  • 2-chloro-1,1,2-trifluoroethyl difluoromethyl ether
  • Alyrane
  • Efrane
  • Enflurane
  • Enflurano
  • Enfluranum
  • Methylflurether
External IDs
  • Anesthetic 347
  • OHIO 347
  • R-E-235CA2

Pharmacology

Indication

Enflurane may be used for both the induction and maintenance of general anesthesia. It can also be used to induce analgesia for vaginal delivery. Low concentrations of enflurane can also be used as an adjunct to general anesthetic drugs during delivery by Cesarean section.18

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Enflurane rapidly induces anesthesia via the stimulation of inhibitory neural channels and the inhibition of excitatory neural channels. Muscle relaxation, obtundation of pharyngeal and laryngeal reflexes, and lowering of blood pressure are some of the main pharmacodynamic effects of this drug.17 Enflurane also decreases cardiac muscle contractility.5

High concentrations of enflurane may lead to uterine relaxation and increase the risk of uterine bleeding during delivery.17 Rare but clinically significant elevations in ALT may indicate hepatoxicity from the use of enflurane.3 In some susceptible patients, enflurane may cause malignant hyperthermia.17

Mechanism of action

The mechanism of action of enflurane is not completely established.17 Studies on rats indicate that enflurane binds to GABAA and glycine receptors, causing depressant effects at the ventral neural horn. It has been reported that 30% of the central nervous system depressant effects on the spinal cord after enflurane is administered are caused by the (GABA-A) receptor while binding to glycine receptors is responsible for about 20 % of the depressant effects.2 The relevance of these findings to humans is unknown. Other studies have found that enflurane binds to the calcium channels in the cardiac sarcoplasmic reticulum causing cardio depressant effects.7,8,9 Other studies support that this drug potentiates glycine receptors, which results in central nervous system depressant effects.12,11

TargetActionsOrganism
AGABA(A) Receptor
potentiator
Humans
UVoltage-gated Potassium Channels
inhibitor
activator
UCalcium-transporting ATPase type 2C member 1
inhibitor
Humans
UGlutamate (NMDA) receptor
antagonist
Humans
USarcoplasmic/endoplasmic reticulum calcium ATPase 1
inhibitor
stimulator
Humans
AVoltage-dependent calcium channel
inhibitor
activator
Humans
AGlycine receptor subunit alpha-1
potentiator
Humans
Absorption

Enflurane is rapidly absorbed into the circulation through the lungs.14,18 The minimum alveolar concentration is oxygen is 1.68%.5

Volume of distribution

Enflurane distributes to the brain, blood, and subcutaneous fat.13

Protein binding

The plasma protein binding for enflurane is 97%.16

Metabolism

Enflurane is metabolized by the CYP2E1 enzyme in the liver to produce inorganic fluoride ions, the major metabolite of enflurane metabolism.10 One reference indicates that enflurane is only 2-5% eliminated after oxidative metabolism in the liver, however more recent evidence suggests that about 9% is eliminated via hepatic oxidation.5

Hover over products below to view reaction partners

Route of elimination

Metabolism accounts for 5-9% of enflurane elimination, sometimes causing nephrotoxicity. Excretion through the skin is believed to be minimal.5

Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

The LD50 of enflurane in rats is 14000 ppm/3 hour(s) when inhaled.20 There is limited information in the literature about enflurane overdose. Hepatotoxicity, cardiotoxicity, nephrotoxicity, and neurotoxicity are expected.18 One report in the literature of an enflurane overdose describes an accidental fatal overdose in a 21-year-old male.13 About 72 hours after death, high amounts of enflurane were found in the brain, blood, and subcutaneous fat. Gas chromatographic studies revealed enflurane concentrations of 350 mg/l-1 in the brain, 130 mg/l-1 in the blood, and 100 mg/l-1 in the subcutaneous fat.13

In the event of an enflurane overdose, immediately stop the administration of enflurane, establish a patent airway, and administer pure oxygen by assisted or controlled ventilation.18

Affected organisms
  • Humans and other mammals
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
AbataceptThe metabolism of Enflurane can be increased when combined with Abatacept.
AcebutololEnflurane may increase the cardiodepressant activities of Acebutolol.
AcetaminophenEnflurane may increase the hepatotoxic activities of Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Enflurane is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Enflurane is combined with Acetophenazine.
AclidiniumEnflurane may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AdalimumabThe metabolism of Enflurane can be increased when combined with Adalimumab.
AdemetionineThe metabolism of Enflurane can be decreased when combined with Ademetionine.
AgomelatineThe risk or severity of adverse effects can be increased when Enflurane is combined with Agomelatine.
AldesleukinThe metabolism of Enflurane can be decreased when combined with Aldesleukin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

International/Other Brands
Alyrane (Baxter) / Compound 347 (Dexa Medica) / Endurane (Singapore Pharmawealth Lifesciences) / Enfluran (Cristália)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnfluraneLiquid99.9 %Respiratory (inhalation)Abbvie1993-12-312012-11-02Canada flag
EthraneLiquid125 mL/125mLRespiratory (inhalation)Baxter Laboratories1972-08-282012-12-01US flag
Ethrane Liq InhLiquidRespiratory (inhalation)Ohmeda Pharmaceutical Products, Division Of Boc Canada Limited1996-09-181997-08-25Canada flag
Ethrane Liquid InhLiquidRespiratory (inhalation)Baxter Laboratories1997-02-202004-08-05Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnfluraneLiquid1 mL/1mLRespiratory (inhalation)Piramal Critical Care Inc1994-07-292014-09-28US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
N01AB04 — Enflurane
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as organofluorides. These are compounds containing a chemical bond between a carbon atom and a fluorine atom.
Kingdom
Organic compounds
Super Class
Organohalogen compounds
Class
Organofluorides
Sub Class
Not Available
Direct Parent
Organofluorides
Alternative Parents
Organooxygen compounds / Organochlorides / Hydrocarbon derivatives / Alkyl fluorides / Alkyl chlorides
Substituents
Aliphatic acyclic compound / Alkyl chloride / Alkyl fluoride / Alkyl halide / Hydrocarbon derivative / Organic oxygen compound / Organochloride / Organofluoride / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organofluorine compound, organochlorine compound, ether (CHEBI:4792)

Chemical Identifiers

UNII
91I69L5AY5
CAS number
13838-16-9
InChI Key
JPGQOUSTVILISH-UHFFFAOYSA-N
InChI
InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H
IUPAC Name
2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
SMILES
FC(F)OC(F)(F)C(F)Cl

References

Synthesis Reference

Terrell, R.C.; U.S. Patents 3,469,011; September 23,1969 and 3,527,813; September 8, 1970; both assigned to Air Reduction Company, Incorporated.

General References
  1. Quail AW: Modern inhalational anaesthetic agents. A review of halothane, isoflurane and enflurane. Med J Aust. 1989 Jan 16;150(2):95-102. [PubMed:2657350]
  2. Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13. [PubMed:16973644]
  3. Authors unspecified: Enflurane . [PubMed:31643793]
  4. Berger JM, Stirt JA, Sullivan SF: Enflurane, halothane, and aminophylline--uptake and pharmacokinetics. Anesth Analg. 1983 Aug;62(8):733-7. [PubMed:6869859]
  5. Dale O, Brown BR Jr: Clinical pharmacokinetics of the inhalational anaesthetics. Clin Pharmacokinet. 1987 Mar;12(3):145-67. doi: 10.2165/00003088-198712030-00001. [PubMed:3555939]
  6. Sleigh JW, Vizuete JA, Voss L, Steyn-Ross A, Steyn-Ross M, Marcuccilli CJ, Hudetz AG: The electrocortical effects of enflurane: experiment and theory. Anesth Analg. 2009 Oct;109(4):1253-62. doi: 10.1213/ANE.0b013e3181add06b. [PubMed:19762755]
  7. Connelly TJ, Coronado R: Activation of the Ca2+ release channel of cardiac sarcoplasmic reticulum by volatile anesthetics. Anesthesiology. 1994 Aug;81(2):459-69. doi: 10.1097/00000542-199408000-00025. [PubMed:8053596]
  8. Eskinder H, Rusch NJ, Supan FD, Kampine JP, Bosnjak ZJ: The effects of volatile anesthetics on L- and T-type calcium channel currents in canine cardiac Purkinje cells. Anesthesiology. 1991 May;74(5):919-26. doi: 10.1097/00000542-199105000-00018. [PubMed:1850580]
  9. Haworth RA, Goknur AB: Inhibition of sodium/calcium exchange and calcium channels of heart cells by volatile anesthestics. Anesthesiology. 1995 May;82(5):1255-65. doi: 10.1097/00000542-199505000-00021. [PubMed:7741301]
  10. Kharasch ED, Thummel KE, Mautz D, Bosse S: Clinical enflurane metabolism by cytochrome P450 2E1. Clin Pharmacol Ther. 1994 Apr;55(4):434-40. doi: 10.1038/clpt.1994.53. [PubMed:8162670]
  11. Krasowski MD, Harrison NL: The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br J Pharmacol. 2000 Feb;129(4):731-43. [PubMed:10683198]
  12. Borghese CM: The molecular pharmacology of volatile anesthetics. Int Anesthesiol Clin. 2015 Spring;53(2):28-39. doi: 10.1097/AIA.0000000000000060. [PubMed:25807016]
  13. Jacob B, Heller C, Daldrup T, Burrig KF, Barz J, Bonte W: Fatal accidental enflurane intoxication. J Forensic Sci. 1989 Nov;34(6):1408-12. [PubMed:2584946]
  14. Torri G: Uptake and elimination of enflurane (Ethrane) at constant inspired and alveolar concentration. Acta Anaesthesiol Belg. 1974 May;25(2):190-7. [PubMed:4440435]
  15. Njoku D, Laster MJ, Gong DH, Eger EI 2nd, Reed GF, Martin JL: Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury. Anesth Analg. 1997 Jan;84(1):173-8. doi: 10.1097/00000539-199701000-00031. [PubMed:8989020]
  16. John D. Current M.D. (n/A). Pharmacology for Anesthetists: anesthesia and adjuvants. N/A.
  17. NIH StatPearls: Enflurane [Link]
  18. FDA Approved Products: Efrane (enflurane) liquid for inhalation [Link]
  19. FDA approval status, Enflurane [Link]
  20. Matheson Gas MSDS: Enflurane [Link]
Human Metabolome Database
HMDB0014373
KEGG Drug
D00543
KEGG Compound
C07516
PubChem Compound
3226
PubChem Substance
46505314
ChemSpider
3113
RxNav
3920
ChEBI
4792
ChEMBL
CHEMBL1257
Therapeutic Targets Database
DAP000799
PharmGKB
PA449461
Wikipedia
Enflurane
MSDS
Download (64.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentAdjunct to general anesthesia therapy1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories hosp products div
  • Piramal critical care inc
  • Baxter healthcare corp anesthesia critical care
Packagers
  • Apothecon
  • Baxter International Inc.
  • Minrad Inc.
  • Rx Elite
Dosage Forms
FormRouteStrength
LiquidRespiratory (inhalation)1 mL/1mL
LiquidRespiratory (inhalation)99.9 %
SolutionRespiratory (inhalation)250 ml
LiquidRespiratory (inhalation)125 mL/125mL
LiquidRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Ethrane inhalation0.55USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)48.5https://www.chemicalbook.com/ChemicalProductProperty_US_CB8437691.aspx
boiling point (°C)56.5Terrell, R.C.; U.S. Patents 3,469,011; September 23,1969 and 3,527,813; September 8, 1970; both assigned to Air Reduction Company, Incorporated.
logP2.10HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility3.9 mg/mLALOGPS
logP2.24ALOGPS
logP2.8ChemAxon
logS-1.7ALOGPS
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity23.07 m3·mol-1ChemAxon
Polarizability9.74 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.994
Caco-2 permeable+0.6125
P-glycoprotein substrateNon-substrate0.8919
P-glycoprotein inhibitor INon-inhibitor0.9553
P-glycoprotein inhibitor IINon-inhibitor0.9297
Renal organic cation transporterNon-inhibitor0.9293
CYP450 2C9 substrateNon-substrate0.8407
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7179
CYP450 1A2 substrateNon-inhibitor0.5701
CYP450 2C9 inhibitorNon-inhibitor0.8112
CYP450 2D6 inhibitorNon-inhibitor0.9408
CYP450 2C19 inhibitorNon-inhibitor0.5794
CYP450 3A4 inhibitorNon-inhibitor0.9604
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8702
Ames testNon AMES toxic0.9132
CarcinogenicityCarcinogens 0.7574
BiodegradationNot ready biodegradable0.9642
Rat acute toxicity1.3804 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9576
hERG inhibition (predictor II)Non-inhibitor0.9032
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.54 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0gb9-9300000000-03817aefdcc06ee54c49
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
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...

Components:
References
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [PubMed:16402123]
  2. Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13. [PubMed:16973644]
  3. Greenblatt EP, Meng X: Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors. Anesthesiology. 2001 Jun;94(6):1026-33. [PubMed:11465594]
  4. ChEMBL Compound Report Card [Link]
  5. NIH StatPearls: Enflurane [Link]
  6. FDA Approved Products: Efrane (enflurane) liquid for inhalation [Link]
Kind
Protein group
Organism
Not Available
Pharmacological action
Unknown
Actions
Inhibitor
Activator
General Function
Voltage-gated potassium channel activity
Specific Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:1990381...

Components:
NameUniProt ID
Potassium voltage-gated channel subfamily A member 1Q09470
Potassium voltage-gated channel subfamily A member 10Q16322
Potassium voltage-gated channel subfamily A member 2P16389
Potassium voltage-gated channel subfamily A member 3P22001
Potassium voltage-gated channel subfamily A member 4P22459
Potassium voltage-gated channel subfamily A member 5P22460
Potassium voltage-gated channel subfamily A member 6P17658
Potassium voltage-gated channel subfamily B member 1Q14721
Potassium voltage-gated channel subfamily B member 2Q92953
Potassium voltage-gated channel subfamily C member 1P48547
Potassium voltage-gated channel subfamily C member 2Q96PR1
Potassium voltage-gated channel subfamily C member 3Q14003
Potassium voltage-gated channel subfamily C member 4Q03721
Potassium voltage-gated channel subfamily D member 1Q9NSA2
Potassium voltage-gated channel subfamily D member 2Q9NZV8
Potassium voltage-gated channel subfamily D member 3Q9UK17
Potassium voltage-gated channel subfamily E member 1P15382
Potassium voltage-gated channel subfamily E member 2Q9Y6J6
Potassium voltage-gated channel subfamily E member 3Q9Y6H6
Potassium voltage-gated channel subfamily E member 4Q8WWG9
Potassium voltage-gated channel subfamily E regulatory beta subunit 5Q9UJ90
Potassium voltage-gated channel subfamily F member 1Q9H3M0
Potassium voltage-gated channel subfamily G member 1Q9UIX4
Potassium voltage-gated channel subfamily G member 2Q9UJ96
Potassium voltage-gated channel subfamily G member 3Q8TAE7
Potassium voltage-gated channel subfamily G member 4Q8TDN1
Potassium voltage-gated channel subfamily H member 1O95259
Potassium voltage-gated channel subfamily H member 2Q12809
Potassium voltage-gated channel subfamily H member 3Q9ULD8
Potassium voltage-gated channel subfamily H member 4Q9UQ05
Potassium voltage-gated channel subfamily H member 5Q8NCM2
Potassium voltage-gated channel subfamily H member 6Q9H252
Potassium voltage-gated channel subfamily H member 7Q9NS40
Potassium voltage-gated channel subfamily H member 8Q96L42
Potassium voltage-gated channel subfamily KQT member 1P51787
Potassium voltage-gated channel subfamily KQT member 2O43526
Potassium voltage-gated channel subfamily KQT member 3O43525
Potassium voltage-gated channel subfamily KQT member 4P56696
Potassium voltage-gated channel subfamily KQT member 5Q9NR82
Potassium voltage-gated channel subfamily S member 1Q96KK3
Potassium voltage-gated channel subfamily S member 3Q9BQ31
Potassium voltage-gated channel subfamily V member 1Q6PIU1
Potassium voltage-gated channel subfamily V member 2Q8TDN2
Voltage-gated potassium channel subunit beta-1Q14722
Voltage-gated potassium channel subunit beta-2Q13303
References
  1. Matchett GA, Allard MW, Martin RD, Zhang JH: Neuroprotective effect of volatile anesthetic agents: molecular mechanisms. Neurol Res. 2009 Mar;31(2):128-34. doi: 10.1179/174313209X393546. [PubMed:19298752]
  2. Friederich P, Benzenberg D, Trellakis S, Urban BW: Interaction of volatile anesthetics with human Kv channels in relation to clinical concentrations. Anesthesiology. 2001 Oct;95(4):954-8. doi: 10.1097/00000542-200110000-00026. [PubMed:11605938]
  3. Namba T, Ishii TM, Ikeda M, Hisano T, Itoh T, Hirota K, Adelman JP, Fukuda K: Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics. Eur J Pharmacol. 2000 Apr 28;395(2):95-101. [PubMed:10794813]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signal transducer activity
Specific Function
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name
ATP2C1
Uniprot ID
P98194
Uniprot Name
Calcium-transporting ATPase type 2C member 1
Molecular Weight
100576.42 Da
References
  1. Kosk-Kosicka D: Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. Adv Pharmacol. 1994;31:313-22. [PubMed:7873420]
  2. Kosk-Kosicka D, Roszczynska G: Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. Anesthesiology. 1993 Oct;79(4):774-80. [PubMed:8214757]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Dildy-Mayfield JE, Eger EI 2nd, Harris RA: Anesthetics produce subunit-selective actions on glutamate receptors. J Pharmacol Exp Ther. 1996 Mar;276(3):1058-65. [PubMed:8786535]
  2. Cheng G, Kendig JJ: Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors. Anesthesiology. 2000 Oct;93(4):1075-84. doi: 10.1097/00000542-200010000-00032. [PubMed:11020764]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Stimulator
Curator comments
Data regarding this target action are limited in the literature.
General Function
Protein homodimerization activity
Specific Function
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP c...
Gene Name
ATP2A1
Uniprot ID
O14983
Uniprot Name
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
Molecular Weight
110251.36 Da
References
  1. Kosk-Kosicka D, Roszczynska G: Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. Anesthesiology. 1993 Oct;79(4):774-80. [PubMed:8214757]
  2. Blanck TJ, Peterson CV, Baroody B, Tegazzin V, Lou J: Halothane, enflurane, and isoflurane stimulate calcium leakage from rabbit sarcoplasmic reticulum. Anesthesiology. 1992 May;76(5):813-21. doi: 10.1097/00000542-199205000-00021. [PubMed:1533495]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Activator
Curator comments
Enflurane has been shown to increase the opening of the calcium channel in cardiac cells during in vitro studies.
General Function
Voltage-gated calcium channel activity
Specific Function
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only...

Components:
NameUniProt ID
Voltage-dependent calcium channel gamma-1 subunitQ06432
Voltage-dependent calcium channel gamma-2 subunitQ9Y698
Voltage-dependent calcium channel gamma-3 subunitO60359
Voltage-dependent calcium channel gamma-4 subunitQ9UBN1
Voltage-dependent calcium channel gamma-5 subunitQ9UF02
Voltage-dependent calcium channel gamma-6 subunitQ9BXT2
Voltage-dependent calcium channel gamma-7 subunitP62955
Voltage-dependent calcium channel gamma-8 subunitQ8WXS5
Voltage-dependent calcium channel subunit alpha-2/delta-1P54289
Voltage-dependent calcium channel subunit alpha-2/delta-2Q9NY47
Voltage-dependent calcium channel subunit alpha-2/delta-3Q8IZS8
Voltage-dependent calcium channel subunit alpha-2/delta-4Q7Z3S7
Voltage-dependent L-type calcium channel subunit alpha-1CQ13936
Voltage-dependent L-type calcium channel subunit alpha-1DQ01668
Voltage-dependent L-type calcium channel subunit alpha-1FO60840
Voltage-dependent L-type calcium channel subunit alpha-1SQ13698
Voltage-dependent L-type calcium channel subunit beta-1Q02641
Voltage-dependent L-type calcium channel subunit beta-2Q08289
Voltage-dependent L-type calcium channel subunit beta-3P54284
Voltage-dependent L-type calcium channel subunit beta-4O00305
Voltage-dependent N-type calcium channel subunit alpha-1BQ00975
Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555
Voltage-dependent R-type calcium channel subunit alpha-1EQ15878
Voltage-dependent T-type calcium channel subunit alpha-1GO43497
Voltage-dependent T-type calcium channel subunit alpha-1HO95180
Voltage-dependent T-type calcium channel subunit alpha-1IQ9P0X4
References
  1. Connelly TJ, Coronado R: Activation of the Ca2+ release channel of cardiac sarcoplasmic reticulum by volatile anesthetics. Anesthesiology. 1994 Aug;81(2):459-69. doi: 10.1097/00000542-199408000-00025. [PubMed:8053596]
  2. Eskinder H, Rusch NJ, Supan FD, Kampine JP, Bosnjak ZJ: The effects of volatile anesthetics on L- and T-type calcium channel currents in canine cardiac Purkinje cells. Anesthesiology. 1991 May;74(5):919-26. doi: 10.1097/00000542-199105000-00018. [PubMed:1850580]
  3. Haworth RA, Goknur AB: Inhibition of sodium/calcium exchange and calcium channels of heart cells by volatile anesthestics. Anesthesiology. 1995 May;82(5):1255-65. doi: 10.1097/00000542-199505000-00021. [PubMed:7741301]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Transmitter-gated ion channel activity
Specific Function
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name
GLRA1
Uniprot ID
P23415
Uniprot Name
Glycine receptor subunit alpha-1
Molecular Weight
52623.35 Da
References
  1. Borghese CM: The molecular pharmacology of volatile anesthetics. Int Anesthesiol Clin. 2015 Spring;53(2):28-39. doi: 10.1097/AIA.0000000000000060. [PubMed:25807016]
  2. Krasowski MD, Harrison NL: The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br J Pharmacol. 2000 Feb;129(4):731-43. [PubMed:10683198]
  3. Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13. [PubMed:16973644]
  4. NIH StatPearls: Enflurane [Link]
  5. ChEMBL Compound Report Card [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Garton KJ, Yuen P, Meinwald J, Thummel KE, Kharasch ED: Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1. Drug Metab Dispos. 1995 Dec;23(12):1426-30. [PubMed:8689955]
  2. Kharasch ED, Thummel KE, Mautz D, Bosse S: Clinical enflurane metabolism by cytochrome P450 2E1. Clin Pharmacol Ther. 1994 Apr;55(4):434-40. doi: 10.1038/clpt.1994.53. [PubMed:8162670]
  3. Njoku D, Laster MJ, Gong DH, Eger EI 2nd, Reed GF, Martin JL: Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury. Anesth Analg. 1997 Jan;84(1):173-8. doi: 10.1097/00000539-199701000-00031. [PubMed:8989020]
  4. Flockhart Table of Drug Interactions [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Liu R, Eckenhoff RG: Weak polar interactions confer albumin binding site selectivity for haloether anesthetics. Anesthesiology. 2005 Apr;102(4):799-805. [PubMed:15791110]
  2. Sawas AH, Pentyala SN, Rebecchi MJ: Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions. Biochemistry. 2004 Oct 5;43(39):12675-85. [PubMed:15449957]
  3. Dale O, Nilsen OG: Displacement of some basic drugs from human serum proteins by enflurane, halothane and their major metabolites. An in vitro study. Br J Anaesth. 1984 May;56(5):535-42. doi: 10.1093/bja/56.5.535. [PubMed:6721962]

Drug created on June 13, 2005 07:24 / Updated on September 03, 2020 19:02

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