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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
Structure for Sevoflurane (DB01236)
- 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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- Contraindications & Blackbox Warnings
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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
Target Actions Organism AGABA(A) Receptor agonistHumans AGlycine receptor subunit alpha-1 agonistHumans AGlutamate receptor 1 antagonistHumans ACalcium transporting ATPases inhibitorHumans AMitochondrial potassium channel activatorHumans UNADH-ubiquinone oxidoreductase chain 1 inhibitorHumans - 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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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/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Voltage-dependent L-type calcium channel subunit alpha-1S --- Not Available c.3257G>A / c.520C>T ADR Inferred Malignant hyperthermia. Details Ryanodine receptor 1 --- Not Available c.103T>C / c.487C>T … show all ADR Inferred Malignant 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Sevoflurane is combined with 1,2-Benzodiazepine. Abaloparatide The risk or severity of adverse effects can be increased when Sevoflurane is combined with Abaloparatide. Abametapir The serum concentration of Sevoflurane can be increased when it is combined with Abametapir. Abatacept The metabolism of Sevoflurane can be increased when combined with Abatacept. Acebutolol Sevoflurane may decrease the antihypertensive activities of Acebutolol. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Sevorane (AbbVie) / Ultane (AbbVie)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sevoflurane Liquid 99.97 % Respiratory (inhalation) Baxter Laboratories 2007-04-11 Not applicable Canada 
Sevoflurane Liquid 99.97 % Respiratory (inhalation) Piramal Critical Care Italia S.P.A. 2009-11-18 Not applicable Canada Sevorane AF Liquid 99.97 % Respiratory (inhalation) Abbvie 1995-12-31 Not applicable Canada Truemed Group LLC Elixir 250 mL/250mL Nasal Truemed Group LLC 2022-09-17 Not applicable US 
Ultane Liquid 250 mL/250mL Respiratory (inhalation) Abbvie 1995-06-07 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sevoflurane Liquid 250 mL/250mL Respiratory (inhalation) Baxter Healthcare Corporation 2002-07-07 Not applicable US Sevoflurane Liquid 250 mL/250mL Respiratory (inhalation) Baxter Healthcare Corporation 2002-07-02 Not applicable US Sevoflurane Liquid 1 mL/1mL Respiratory (inhalation) NextSource Pharma 2024-02-21 Not applicable US Sevoflurane Liquid 250 mL/250mL Respiratory (inhalation) Lannett Company, Inc. 2023-08-18 Not applicable US Sevoflurane Liquid 1 mL/1mL Respiratory (inhalation) Piramal Critical Care Italia S.P.A. 2020-10-01 Not applicable US
Categories
- ATC Codes
- N01AB08 — Sevoflurane
- Drug Categories
- Agents that produce hypertension
- Anesthetics
- Anesthetics, General
- Anesthetics, Inhalation
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Ethers
- Hydrocarbons, Fluorinated
- Hydrocarbons, Halogenated
- Hypotensive Agents
- Methyl Ethers
- Nervous System
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: Ultane (sevoflurane), volatile liquid for inhalation [Link]
- Cayman chemical: Sevoflurane SDS [Link]
- External Links
- Human Metabolome Database
- HMDB0015366
- KEGG Drug
- D00547
- KEGG Compound
- C07520
- PubChem Compound
- 5206
- PubChem Substance
- 46508591
- ChemSpider
- 5017
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Other Anesthesia and Neurotoxicity 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Prevention Alzheimer's Disease (AD) / Dementia 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Prevention Anesthesia therapy / Colon Cancer 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Prevention Anesthesia therapy / Colorectal Cancer 1 somestatus stop reason just information to hide Not Available Completed Not Available Airway Management During Operative Procedure 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Abbott Laboratories Ltd.
- Baxter International Inc.
- Hospira Inc.
- Minrad Inc.
- Rx Elite
- Dosage Forms
Form Route Strength Solution Respiratory (inhalation) 250.000 mL Solution Respiratory (inhalation) 1.00 mL Aerosol Respiratory (inhalation) 1 ml/1ml Solution Respiratory (inhalation) Solution Respiratory (inhalation) 100 % Liquid Respiratory (inhalation) 100 % Aerosol Respiratory (inhalation) 250 ML Liquid Respiratory (inhalation) 1 mL/1mL Liquid Respiratory (inhalation) 250 mL/250mL Aerosol Respiratory (inhalation) 1 ML/ML Inhalant Respiratory (inhalation) 1 mL/1mL Inhalant Respiratory (inhalation) 1 ml/ml Liquid Respiratory (inhalation) 250 ml Solution Respiratory (inhalation) 100 mL Inhalant Respiratory (inhalation) 100 % Inhalant Respiratory (inhalation) 250 ML Solution Nasal 100.000 mL Solution Respiratory (inhalation) 100 ml/100ml Liquid Respiratory (inhalation) Liquid Respiratory (inhalation) 99.97 % Solution Nasal 100 % Liquid Respiratory (inhalation) 100 % v/v Solution Respiratory (inhalation) 250 ml Inhalant Respiratory (inhalation) 100 % v/v Solution Respiratory (inhalation) 100.000 mL Elixir Nasal 250 mL/250mL Solution Respiratory (inhalation) 100.00 mL - Prices
Unit description Cost Unit Ultane 250 ml pen bottle 1.16USD ml Sojourn inhalation liquid 0.99USD ml Sevoflurane inhalation liquid 0.89USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6288127 Yes 2001-09-11 2017-07-27 US US5990176 Yes 1999-11-23 2017-07-27 US US6074668 Yes 2000-06-13 2018-07-09 US US6444859 Yes 2002-09-03 2017-07-27 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) < 25 °C PhysProp boiling point (°C) 58.5 °C PhysProp and Behne M, et al. Clin Pharmacokinet. 1999;36(1):13-26. water solubility Very slightly soluble Not Available logP 2.4 Not Available - Predicted Properties
Property Value Source Water Solubility 1.48 mg/mL ALOGPS logP 2.44 ALOGPS logP 2.27 Chemaxon logS -2.1 ALOGPS pKa (Strongest Acidic) 15.07 Chemaxon pKa (Strongest Basic) -4.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 9.23 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 23.3 m3·mol-1 Chemaxon Polarizability 9.83 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9963 Blood Brain Barrier + 0.9941 Caco-2 permeable + 0.6134 P-glycoprotein substrate Non-substrate 0.8839 P-glycoprotein inhibitor I Non-inhibitor 0.8807 P-glycoprotein inhibitor II Non-inhibitor 0.5436 Renal organic cation transporter Non-inhibitor 0.8649 CYP450 2C9 substrate Non-substrate 0.9039 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.6876 CYP450 1A2 substrate Inhibitor 0.5254 CYP450 2C9 inhibitor Non-inhibitor 0.7941 CYP450 2D6 inhibitor Non-inhibitor 0.9114 CYP450 2C19 inhibitor Inhibitor 0.5569 CYP450 3A4 inhibitor Non-inhibitor 0.9148 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7006 Ames test AMES toxic 0.5082 Carcinogenicity Carcinogens 0.7014 Biodegradation Not ready biodegradable 0.8564 Rat acute toxicity 1.3361 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9485 hERG inhibition (predictor II) Non-inhibitor 0.8685
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0f89-6900000000-783322b6f193100b0153 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0090000000-dd5de4e1c85006607a94 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-f86a9f10b8af17df6b37 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0090000000-162bc699ad52e7fdb702 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-9ec740871fceeffeeb4b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-1900000000-91f1acbf6edf68e78eed Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-95df4dc9461c5dfff817 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 111.0849656 predictedDarkChem Lite v0.1.0 [M-H]- 134.08899 predictedDeepCCS 1.0 (2019) [M+H]+ 112.0683656 predictedDarkChem Lite v0.1.0 [M+H]+ 136.44627 predictedDeepCCS 1.0 (2019) [M+Na]+ 111.3581656 predictedDarkChem Lite v0.1.0 [M+Na]+ 144.98158 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- 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
Components:
References
- Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
- 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
- Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:14551753, PubMed:16144831, PubMed:2155780, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:7920629, PubMed:9009272). Channel opening is also triggered by taurine and beta-alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity)
- Specific Function
- extracellularly glycine-gated chloride channel activity
- Gene Name
- GLRA1
- Uniprot ID
- P23415
- Uniprot Name
- Glycine receptor subunit alpha-1
- Molecular Weight
- 52623.35 Da
References
- Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
- 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
- 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:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). 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 upon entry of monovalent and divalent cations such as sodium and calcium. 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 CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)
- Specific Function
- adenylate cyclase binding
- Gene Name
- GRIA1
- Uniprot ID
- P42261
- Uniprot Name
- Glutamate receptor 1
- Molecular Weight
- 101505.245 Da
References
- Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0. [Article]
- 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
- ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:12707275, PubMed:16192278, PubMed:20439740, PubMed:21187401, PubMed:30923126). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:16192278, PubMed:16332677, PubMed:30923126). Plays a primary role in the maintenance of Ca(2+) homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology (PubMed:14632183, PubMed:20439740). Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (PubMed:10615129, PubMed:14632183, PubMed:20439740). Participates in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity (By similarity). May also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity (PubMed:21187401)
- Specific Function
- ATP binding
Components:
References
- Lopez MM, Kosk-Kosicka D: How do volatile anesthetics inhibit Ca(2+)-ATPases? J Biol Chem. 1995 Nov 24;270(47):28239-45. [Article]
- 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]
- 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]
- 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
- Yes
- Actions
- Activator
- General Function
- Pore-forming subunit of the mitochondrial ATP-gated potassium channel (mitoK(ATP)) (PubMed:31435016). Together with ATP-binding subunit ABCB8/MITOSUR of the mitoK(ATP) channel, mediates ATP-dependent K(+) currents across the mitochondrial inner membrane (PubMed:31435016). An increase in ATP intracellular levels closes the channel, inhibiting K(+) transport, whereas a decrease in ATP levels enhances K(+) uptake in the mitochondrial matrix. 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
- 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]
- 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]
- 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]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:1959619). Essential for the catalytic activity and assembly of complex I (PubMed:1959619, PubMed:26929434)
- Specific Function
- NADH dehydrogenase (ubiquinone) activity
- Gene Name
- MT-ND1
- Uniprot ID
- P03886
- Uniprot Name
- NADH-ubiquinone oxidoreductase chain 1
- Molecular Weight
- 35660.055 Da
References
- 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]
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
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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 epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- 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]
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Kharasch ED: Biotransformation of sevoflurane. Anesth Analg. 1995 Dec;81(6 Suppl):S27-38. doi: 10.1097/00000539-199512001-00005. [Article]
- 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]
- 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]
- 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]
- 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
- 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. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56517.005 Da
References
- 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]
- 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
- 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
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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]
- 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
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- 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 October 29, 2024 14:47