Identification

Summary

Sevoflurane is a inhalation anaesthetic agent used for induction and maintenance of general anesthesia during surgical procedures.

Brand Names
Sevorane, Sojourn, Ultane
Generic Name
Sevoflurane
DrugBank Accession Number
DB01236
Background

Sevoflurane is an ether inhalation anesthetic agent used to induce and maintain general anesthesia.8 It is a volatile, non-flammable compound with a low solubility profile and blood/gas partition coefficient.8 Sevoflurane was patented in 1972, was approved for clinical use in Japan in 1990, and approved by the FDA in 1996.1 Sevoflurane is three times more potent than desflurane, but has lower potency compared to halothane and isoflurane. Unlike other volatile anesthetics, sevoflurane has a pleasant odor and does not irritate the airway. The hemodynamic and respiratory depressive effects of sevoflurane are well tolerated, and most patients receiving this anesthetic agent present little toxicity.7 Therefore, it can be used for inhalational induction in adults and children for a wide variety of anesthetic procedures.1

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Weight
Average: 200.0548
Monoisotopic: 200.007212153
Chemical Formula
C4H3F7O
Synonyms
  • 1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propane
  • Sevofluran
  • Sevoflurane
  • Sevoflurano
  • Sevofluranum
External IDs
  • MR-6S4
  • MR6S4

Pharmacology

Indication

Sevoflurane is used for the induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.8

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Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Sevoflurane induces muscle relaxation and reduces sensitivity by altering tissue excitability with a fast onset of action. It does so by decreasing the extent of gap junction-mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.6 Compared to halothane and isoflurane, sevoflurane has a shorter emergence time, as well as a shorter time to first analgesia.8 To reach an equilibrium between alveolar and arterial partial pressure, only a minimal amount of sevoflurane needs to be dissolved in blood.8

The use of sevoflurane can increase the risk of renal injury, respiratory depression, and QT prolongation. Also, it can lead to malignant hyperthermia, perioperative hyperkalemia, and pediatric neurotoxicity. Episodes of severe bradycardia and cardiac arrest have been reported in pediatric patients with Down Syndrome given sevoflurane. Sevoflurane anesthesia may impair the performance of activities requiring mental alertness, such as driving or operating machinery.8

Mechanism of action

The precise mechanism of action of sevoflurane has not been fully elucidated. Like other halogenated inhalational anesthetics, sevoflurane induces anesthesia by binding to ligand-gated ion channels and blocking CNS neurotransmission. It has been suggested that inhaled anesthetics enhance inhibitory postsynaptic channel activity by binding GABAA and glycine receptors, and inhibit excitatory synaptic channel activity by binding nicotinic acetylcholine, serotonin, and glutamate receptors.3 Sevoflurane has an effect on several ionic currents, including the hyperpolarisation-activated cation current (If), the T-type and L-type Ca2+ currents (ICa, T and ICa, L), the slowly activating delayed rectifier K+ currents (IKs), and the Na+/Ca2+ exchange current (INCX).4 This ability to modulate ion channel activity can also regulate cardiac excitability and contractility.4

TargetActionsOrganism
AGABA(A) Receptor
agonist
Humans
AGlycine receptor subunit alpha-1
agonist
Humans
AGlutamate receptor 1
antagonist
Humans
ACalcium transporting ATPases
inhibitor
Humans
UNADH-ubiquinone oxidoreductase chain 1
inhibitor
Humans
AMitochondrial potassium channel
activator
Humans
Absorption

Sevoflurane is rapidly absorbed into circulation through the lungs; however, solubility in the blood is low (blood/gas partition coefficient at 37°C ranges from 0.63 to 0.69).8 Therefore, a minimal amount of sevoflurane needs to be dissolved in blood in order to induce anesthesia.1

Volume of distribution

Patients given low-flow sevoflurane anesthesia during maxillofacial surgery (n=16) had a peripheral volume of distribution of 1634 mlvapour/kgbw and a total volume of distribution of 1748 mlvapour/kgbw.2

Protein binding

Sevoflurane protein binding has not been evaluated. In vitro analyses have shown that other fluorinated volatile anesthetics can displace drugs from serum and tissue proteins; however, it is unclear if this is clinically significant. Clinical studies have shown that the administration of sevoflurane does not have a significant effect in patients taking drugs that are highly bound and have a small volume of distribution.8

Metabolism

Sevoflurane is metabolized to hexafluoroisopropanol by cytochrome P450 2E1 in a reaction that promotes the release of inorganic fluoride and carbon dioxide. Hexafluoroisopropanol is rapidly conjugated with glucuronic acid and eliminated in urine. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized.8 In most cases, inorganic fluoride reaches its highest concentration within 2 hours of the end of sevoflurane anesthesia, and returns to baseline levels within 48 hours. Sevoflurane metabolism may be induced by chronic exposure to isoniazid and ethanol, and it has been shown that barbiturates do not affect it.8

Hover over products below to view reaction partners

Route of elimination

The low solubility of sevoflurane facilitates its rapid elimination through the lungs, where 95% to 98% of this anesthetic is eliminated.1,8 Up to 3.5% of the sevoflurane dose appears in urine as inorganic fluoride, and as much as 50% of fluoride clearance is nonrenal (fluoride taken up into bone).8

Half-life

The terminal elimination half-life of sevoflurane from the peripheral fat compartment is approximately 20 hours.1

Clearance

In patients given low-flow sevoflurane anaesthesia during maxillofacial surgery (n=16), the transport clearance from the central to the peripheral compartment was 13.0 mlvapour/kgbw⋅min.2

Adverse Effects
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Toxicity

In the event of sevoflurane overdosage (or what may appear to be overdosage) discontinue administration, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.8 Patients experiencing an overdose may be at an increased risk of severe adverse effects such as renal injury, respiratory depression, severe bradycardia and cardiac arrest. Fatalities due to sevoflurane abuse have been reported as well.5 Symptomatic and supportive measures are recommended. Animal studies have shown that the use of anesthetic agents during periods of rapid brain growth or synaptogenesis results in alterations in synaptic morphology and neurogenesis. In primates, anesthetic regimens of up to 3 hours did not increase neuronal cell loss, but regimens of 5 hours or longer did have a significant effect.8 The oral LD50 of sevoflurane is 10.8 g/kg in rats and 18.2 g/kg in mice.9

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Voltage-dependent L-type calcium channel subunit alpha-1S---Not Availablec.3257G>A / c.520C>TADR InferredMalignant hyperthermia.Details
Ryanodine receptor 1---Not Availablec.103T>C / c.487C>T  … show all ADR InferredMalignant hyperthermia.Details

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 adverse effects can be increased when Sevoflurane is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Sevoflurane can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Sevoflurane can be increased when combined with Abatacept.
AcebutololSevoflurane may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Sevoflurane is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Sevoflurane is combined with Acemetacin.
AcetaminophenSevoflurane may increase the hepatotoxic activities of Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Sevoflurane.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Sevoflurane.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Acetylsalicylic acid is combined with Sevoflurane.
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Food Interactions
No interactions found.

Products

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International/Other Brands
Sevorane (AbbVie) / Ultane (AbbVie)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SevofluraneLiquid99.97 %Respiratory (inhalation)Piramal Critical Care Inc2009-11-18Not applicableCanada flag
SevofluraneLiquid99.97 %Respiratory (inhalation)Baxter Laboratories2007-04-11Not applicableCanada flag
Sevorane AFLiquid99.97 %Respiratory (inhalation)Abbvie1995-12-31Not applicableCanada flag
Truemed Group LLCElixir250 mL/250mLNasalTruemed Group LLC2022-09-17Not applicableUS flag
UltaneLiquid250 mL/250mLRespiratory (inhalation)AbbVie Inc.1995-06-07Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SevofluraneLiquid1 mL/1mLRespiratory (inhalation)Piramal Critical Care Inc2020-10-01Not applicableUS flag
SevofluraneLiquid250 mL/250mLRespiratory (inhalation)Baxter Healthcare Corporation2002-07-07Not applicableUS flag
SevofluraneLiquid1 mL/1mLRespiratory (inhalation)Piramal Critical Care Inc2011-07-15Not applicableUS flag
SevofluraneLiquid1 mL/1mLRespiratory (inhalation)Halocarbon Life Sciences, LLC2007-11-19Not applicableUS flag
SevofluraneLiquid250 mL/250mLRespiratory (inhalation)Sandoz Inc.2017-01-25Not applicableUS flag
SevofluraneLiquid250 mL/250mLRespiratory (inhalation)Baxter Healthcare Corporation2002-07-02Not applicableUS flag
Sevoflurane BostonbioInhalant1 mL/1mLRespiratory (inhalation)Boston Biopharma2020-03-27Not applicableUS flag
SojournLiquid1 mL/1mLRespiratory (inhalation)Piramal Critical Care Inc2010-04-13Not applicableUS flag

Categories

ATC Codes
N01AB08 — Sevoflurane
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dialkyl ethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are alkyl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Dialkyl ethers
Alternative Parents
Organofluorides / Hydrocarbon derivatives / Alkyl fluorides
Substituents
Aliphatic acyclic compound / Alkyl fluoride / Alkyl halide / Dialkyl ether / Hydrocarbon derivative / Organofluoride / Organohalogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organofluorine compound, ether (CHEBI:9130)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
38LVP0K73A
CAS number
28523-86-6
InChI Key
DFEYYRMXOJXZRJ-UHFFFAOYSA-N
InChI
InChI=1S/C4H3F7O/c5-1-12-2(3(6,7)8)4(9,10)11/h2H,1H2
IUPAC Name
1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane
SMILES
FCOC(C(F)(F)F)C(F)(F)F

References

Synthesis Reference

Terrell, RC., et al. (1999) Method for the preparation of sevoflurane (U.S. Patent US 5,969,193). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/76/64/1d/83a9d1ed707307/US5969193.pdf

US5969193
General References
  1. Behne M, Wilke HJ, Harder S: Clinical pharmacokinetics of sevoflurane. Clin Pharmacokinet. 1999 Jan;36(1):13-26. doi: 10.2165/00003088-199936010-00002. [Article]
  2. Wissing H, Kuhn I, Rietbrock S, Fuhr U: Pharmacokinetics of inhaled anaesthetics in a clinical setting: comparison of desflurane, isoflurane and sevoflurane. Br J Anaesth. 2000 Apr;84(4):443-9. doi: 10.1093/oxfordjournals.bja.a013467. [Article]
  3. Campagna JA, Miller KW, Forman SA: Mechanisms of actions of inhaled anesthetics. N Engl J Med. 2003 May 22;348(21):2110-24. doi: 10.1056/NEJMra021261. [Article]
  4. Kojima A, Matsuura H: Ionic mechanisms of the action of anaesthetics on sinoatrial node automaticity. Eur J Pharmacol. 2017 Nov 5;814:63-72. doi: 10.1016/j.ejphar.2017.08.006. Epub 2017 Aug 9. [Article]
  5. Levine B, Cox D, Jufer-Phipps RA, Li L, Jacobs A, Fowler D: A fatality from sevoflurane abuse. J Anal Toxicol. 2007 Oct;31(8):534-6. doi: 10.1093/jat/31.8.534. [Article]
  6. Masaki E, Kawamura M, Kato F: Attenuation of gap-junction-mediated signaling facilitated anesthetic effect of sevoflurane in the central nervous system of rats. Anesth Analg. 2004 Mar;98(3):647-52, table of contents. doi: 10.1213/01.ane.0000103259.72635.72. [Article]
  7. Michel F, Constantin JM: Sevoflurane inside and outside the operating room. Expert Opin Pharmacother. 2009 Apr;10(5):861-73. doi: 10.1517/14656560902798752. [Article]
  8. FDA Approved Drug Products: Ultane (sevoflurane), volatile liquid for inhalation [Link]
  9. Cayman chemical: Sevoflurane SDS [Link]
Human Metabolome Database
HMDB0015366
KEGG Drug
D00547
KEGG Compound
C07520
PubChem Compound
5206
PubChem Substance
46508591
ChemSpider
5017
RxNav
36453
ChEBI
9130
ChEMBL
CHEMBL1200694
ZINC
ZINC000001530810
Therapeutic Targets Database
DAP000694
PharmGKB
PA451341
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sevoflurane

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableNoncardiac Surgery1
4CompletedBasic ScienceAnesthesia therapy / Loss of Consciousness1
4CompletedBasic ScienceAortic Diseases / Valvular Heart Disease1
4CompletedBasic ScienceHealthy Subjects (HS)1
4CompletedBasic ScienceRenal Cancers / Surgery1
4CompletedBasic ScienceSevoflurane Anesthesia1
4CompletedDiagnosticAdenotonsillectomy / Emergence Delirium / Postoperative pain1
4CompletedDiagnosticAnesthesia therapy / Electroencephalography/Drug Effects1
4CompletedDiagnosticAuditory Dysfunction, Central / Cognitive Dysfunctions1
4CompletedDiagnosticAwareness During General Anesthesia / Inhalation; Gas / Recall phenomenon1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Baxter International Inc.
  • Hospira Inc.
  • Minrad Inc.
  • Rx Elite
Dosage Forms
FormRouteStrength
SolutionRespiratory (inhalation)100 %
AerosolRespiratory (inhalation)1 ml/1ml
AerosolRespiratory (inhalation)250 ML
LiquidRespiratory (inhalation)100 %
AerosolRespiratory (inhalation)
LiquidRespiratory (inhalation)1 mL/1mL
LiquidRespiratory (inhalation)250 mL/250mL
InhalantRespiratory (inhalation)1 mL/1mL
InhalantRespiratory (inhalation)1 ml/ml
LiquidRespiratory (inhalation)250 ml
SolutionRespiratory (inhalation)100 mL
InhalantRespiratory (inhalation)100 %
InhalantRespiratory (inhalation)250 ML
SolutionRespiratory (inhalation)
SolutionRespiratory (inhalation)100 ml/100ml
LiquidRespiratory (inhalation)
LiquidRespiratory (inhalation)99.97 %
SolutionNasal100 %
LiquidRespiratory (inhalation)100 % v/v
InhalantRespiratory (inhalation)100 % v/v
ElixirNasal250 mL/250mL
Prices
Unit descriptionCostUnit
Ultane 250 ml pen bottle1.16USD ml
Sojourn inhalation liquid0.99USD ml
Sevoflurane inhalation liquid0.89USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6288127Yes2001-09-112017-07-27US flag
US5990176Yes1999-11-232017-07-27US flag
US6074668Yes2000-06-132018-07-09US flag
US6444859Yes2002-09-032017-07-27US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)58.5 °CPhysProp and Behne M, et al. Clin Pharmacokinet. 1999;36(1):13-26.
water solubilityVery slightly solubleNot Available
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.48 mg/mLALOGPS
logP2.44ALOGPS
logP2.27ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)15.07ChemAxon
pKa (Strongest Basic)-4.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity23.3 m3·mol-1ChemAxon
Polarizability9.83 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9963
Blood Brain Barrier+0.9941
Caco-2 permeable+0.6134
P-glycoprotein substrateNon-substrate0.8839
P-glycoprotein inhibitor INon-inhibitor0.8807
P-glycoprotein inhibitor IINon-inhibitor0.5436
Renal organic cation transporterNon-inhibitor0.8649
CYP450 2C9 substrateNon-substrate0.9039
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6876
CYP450 1A2 substrateInhibitor0.5254
CYP450 2C9 inhibitorNon-inhibitor0.7941
CYP450 2D6 inhibitorNon-inhibitor0.9114
CYP450 2C19 inhibitorInhibitor0.5569
CYP450 3A4 inhibitorNon-inhibitor0.9148
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7006
Ames testAMES toxic0.5082
CarcinogenicityCarcinogens 0.7014
BiodegradationNot ready biodegradable0.8564
Rat acute toxicity1.3361 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9485
hERG inhibition (predictor II)Non-inhibitor0.8685
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

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Kind
Protein group
Organism
Humans
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...

Components:
References
  1. Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
  2. Brohan J, Goudra BG: The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017 Oct;31(10):845-856. doi: 10.1007/s40263-017-0463-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
  2. Campagna JA, Miller KW, Forman SA: Mechanisms of actions of inhaled anesthetics. N Engl J Med. 2003 May 22;348(21):2110-24. doi: 10.1056/NEJMra021261. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Pdz domain binding
Specific Function
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a co...
Gene Name
GRIA1
Uniprot ID
P42261
Uniprot Name
Glutamate receptor 1
Molecular Weight
101505.245 Da
References
  1. Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
  2. Campagna JA, Miller KW, Forman SA: Mechanisms of actions of inhaled anesthetics. N Engl J Med. 2003 May 22;348(21):2110-24. doi: 10.1056/NEJMra021261. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
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.

Components:
References
  1. Lopez MM, Kosk-Kosicka D: How do volatile anesthetics inhibit Ca(2+)-ATPases? J Biol Chem. 1995 Nov 24;270(47):28239-45. [Article]
  2. Pinheiro AC, Gomez RS, Guatimosim C, Silva JH, Prado MA, Gomez MV: The effect of sevoflurane on intracellular calcium concentration from cholinergic cells. Brain Res Bull. 2006 Mar 31;69(2):147-52. doi: 10.1016/j.brainresbull.2005.11.016. Epub 2005 Dec 19. [Article]
  3. Liu TJ, Zhang JC, Gao XZ, Tan ZB, Wang JJ, Zhang PP, Cheng AB, Zhang SB: Effect of sevoflurane on the ATPase activity of hippocampal neurons in a rat model of cerebral ischemia-reperfusion injury via the cAMP-PKA signaling pathway. Kaohsiung J Med Sci. 2018 Jan;34(1):22-33. doi: 10.1016/j.kjms.2017.09.004. Epub 2017 Nov 14. [Article]
  4. Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nadh dehydrogenase (ubiquinone) activity
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
MT-ND1
Uniprot ID
P03886
Uniprot Name
NADH-ubiquinone oxidoreductase chain 1
Molecular Weight
35660.055 Da
References
  1. La Monaca E, Fodale V: Effects of anesthetics on mitochondrial signaling and function. Curr Drug Saf. 2012 Apr;7(2):126-39. doi: 10.2174/157488612802715681. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Activator
General Function
Mitochondrial potassium channel located in the mitochondrial inner membrane (PubMed:31435016). Together with ABCB8/MITOSUR, forms a protein complex localized in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane (that is, mitoK(ATP) channel) (PubMed:31435016). May contribute to the homeostatic control of cellular metabolism under stress conditions by regulating the mitochondrial matrix volume (PubMed:31435016).
Specific Function
Mitochondrial atp-gated potassium channel activity
Gene Name
CCDC51
Uniprot ID
Q96ER9
Uniprot Name
Mitochondrial potassium channel
Molecular Weight
45810.91 Da
References
  1. La Monaca E, Fodale V: Effects of anesthetics on mitochondrial signaling and function. Curr Drug Saf. 2012 Apr;7(2):126-39. doi: 10.2174/157488612802715681. [Article]
  2. Adamczyk S, Robin E, Simerabet M, Kipnis E, Tavernier B, Vallet B, Bordet R, Lebuffe G: Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial K ATP channel. Br J Anaesth. 2010 Feb;104(2):191-200. doi: 10.1093/bja/aep365. [Article]
  3. Wang JK, Wu HF, Zhou H, Yang B, Liu XZ: Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury involving mitochondrial ATP-dependent potassium channel and mitochondrial permeability transition pore. Neurol Res. 2015 Jan;37(1):77-83. doi: 10.1179/1743132814Y.0000000410. Epub 2014 Jun 25. [Article]
  4. Ye Z, Guo Q, Wang N, Xia P, Yuan Y, Wang E: Delayed neuroprotection induced by sevoflurane via opening mitochondrial ATP-sensitive potassium channels and p38 MAPK phosphorylation. Neurol Sci. 2012 Apr;33(2):239-49. doi: 10.1007/s10072-011-0665-6. Epub 2011 Jul 1. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Compared to CYP2E1, CYP2A6 and CYP3A4, CYP2B6 had higher activity for the defluorination of sevoflurane.
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Kharasch ED, Hankins DC, Thummel KE: Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. Anesthesiology. 1995 Mar;82(3):689-99. doi: 10.1097/00000542-199503000-00011. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Compared to CYP2A6 and CYP3A4, CYP2E1 had higher activity for the defluorination of sevoflurane, and a lower activity compared to CYP2B6.
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. Kharasch ED: Biotransformation of sevoflurane. Anesth Analg. 1995 Dec;81(6 Suppl):S27-38. doi: 10.1097/00000539-199512001-00005. [Article]
  2. Wandel C, Neff S, Keppler G, Bohrer H, Stockinger K, Wilkinson GR, Wood M, Martin E: The relationship between cytochrome P4502E1 activity and plasma fluoride levels after sevoflurane anesthesia in humans. Anesth Analg. 1997 Oct;85(4):924-30. doi: 10.1097/00000539-199710000-00038. [Article]
  3. Kharasch ED, Thummel KE: Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology. 1993 Oct;79(4):795-807. [Article]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Compared to CYP3A4, CYP2A6 had higher activity for the defluorination of sevoflurane, and a lower activity compared to CYP2B6 and CYP2E1.
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  2. Kharasch ED, Hankins DC, Thummel KE: Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. Anesthesiology. 1995 Mar;82(3):689-99. doi: 10.1097/00000542-199503000-00011. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Compared to CYP2B6, CYP2E1 and CYP2A6, CYP3A4 had lower activity for the defluorination of sevoflurane.
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kharasch ED, Hankins DC, Thummel KE: Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. Anesthesiology. 1995 Mar;82(3):689-99. doi: 10.1097/00000542-199503000-00011. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

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. 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. [Article]

Drug created at June 13, 2005 13:24 / Updated at September 27, 2022 08:31