Desflurane (T3D3013)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (8)XML
Targets (8)
Record Information
Version2.0
Creation Date2009-07-21 20:28:35 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3013
Identification
Common NameDesflurane
ClassSmall Molecule
DescriptionDesflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anaesthesia. Volatile agents such as desflurane may activate GABA channels and hyperpolarize cell membranes. In addition, they may inhibit certain calcium channels and therefore prevent release of neurotransmitters and inhibit glutamate channels. Volatile anesthetics easily partition into cellular membranes and could expand the volume of the cell membrane and subsequently distort channels necessary for sodium ion flux and the development of action potentials necessary for synaptic transmission. Desflurane preconditions human myocardium against ischemia through activation of mitochondrial K(ATP) channels, adenosine A1 receptor, and alpha and beta adrenoceptors.
Compound Type
  • Anesthetic, Inhalation
  • Drug
  • Metabolite
  • Neuroprotective Agent
  • Organic Compound
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(+-)-2-Difluoromethyl 1,2,2,2-tetrafluoroethyl ether
1,1,1,2-Tetrafluoro-2-(difluoromethoxy)ethane
Desflurano
Desfluranum
Difluoromethyl 1,2,2,2-tetrafluoroethyl ether
Suprane
Chemical FormulaC3H2F6O
Average Molecular Mass168.038 g/mol
Monoisotopic Mass168.001 g/mol
CAS Registry Number57041-67-5
IUPAC Name2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane
Traditional Namedesflurane
SMILESFC(F)OC(F)C(F)(F)F
InChI IdentifierInChI=1/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H
InChI KeyInChIKey=DPYMFVXJLLWWEU-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as organofluorides. Organofluorides are compounds containing a chemical bond between a carbon atom and a fluorine atom.
KingdomOrganic compounds
Super ClassOrganohalogen compounds
ClassOrganofluorides
Sub ClassNot Available
Direct ParentOrganofluorides
Alternative Parents
Substituents
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Alkyl halide
  • Alkyl fluoride
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateGas
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling Point23.5°C
SolubilityNegligible
LogP1.9
Predicted Properties
PropertyValueSource
Water Solubility3.54 g/LALOGPS
logP2.19ALOGPS
logP2.4ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)18.87ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity18.12 m³·mol⁻¹ChemAxon
Polarizability7.89 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-9400000000-9bfc58e3ef0acdde70c62017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-cb928c5773584b51d8f92016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0900000000-908513735b5ab0dbea3b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9400000000-293244954cfd93a152242016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-14d2d394901471ee6fe92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014j-0900000000-90d14c3cc1002cc1c1e12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6t-4900000000-ce5b2fc5da9d94a0bb542016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-621e6be94ab63a3ea3552021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0900000000-1e30f1fadbc21bfcdc252021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kb-4900000000-4bc2f4f843987f1be78e2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-b3181a2326303b91e3bf2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-1900000000-38f9e805bae921315c8d2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-0900000000-b3181a2326303b91e3bf2021-10-11View Spectrum
Toxicity Profile
Route of ExposureRapidly absorbed into the circulation via the lungs following inhalation.
Mechanism of ToxicityDesflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Desflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Desflurane also binds to and agonizes the GABA receptor, the large conductance Ca2+ activated potassium channel, the glycine receptors, and antagonizes the glutamate receptors.
MetabolismMinimally biotransformed in the liver in humans (approximately 0.02% of the quantity absorbed).
Toxicity ValuesLD50: 312.0 mg.kg-1 (i.v,swiss rate) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed for maintenance of general anesthesia. Due to this airway irritability, Desflurane is infrequently used to induce anesthesia via inhalation techniques. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsIt may cause tachycardia and airway irritability when administered at concentrations greater than 10 vol%. [Wikipedia]
SymptomsNot Available
TreatmentIn the event of overdosage, or suspected overdosage, take the following actions: discontinue administration of Desflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01189
HMDB IDHMDB15320
PubChem Compound ID42113
ChEMBL IDCHEMBL1200733
ChemSpider ID38403
KEGG IDC07519
UniProt IDNot Available
OMIM ID
ChEBI ID4445
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDesflurane
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDesflurane
References
Synthesis Reference

Leonid A. Rozov, Chialang Huang, Gerald G. Vernice, “Synthesis of desflurane.” U.S. Patent US5205914, issued June, 1991.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, Shigematsu A: The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes. Pharmacology. 2006;77(2):93-9. Epub 2006 May 5. [16679816 ]
  3. Anesthetic and Hemodynamic Effects of Desflurane Lipid Emulsion. Gisele Zapata-Sudo, M.D., Ph.D., Maria A. Abrão, M.D., Margarete M. Trachez, M.D., Ph.D., Roberto T. Sudo, M.D., Ph.D.
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. GABA-A receptor (anion channel) (Protein Group)
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [11752090 ]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [18384456 ]
Target Details
2. ATP synthase subunit delta, mitochondrial
General Function:
Transporter activity
Specific Function:
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
Gene Name:
ATP5D
Uniprot ID:
P30049
Molecular Weight:
17489.755 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
3. Calcium-transporting ATPase type 2C member 1
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
Molecular Weight:
100576.42 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
4. Gamma-aminobutyric acid receptor subunit alpha-1
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
5. Glutamate receptor 1
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 conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA1
Uniprot ID:
P42261
Molecular Weight:
101505.245 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
6. Glycine receptor subunit alpha-1
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
Molecular Weight:
52623.35 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
7. NADH-ubiquinone oxidoreductase chain 1
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 transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Gene Name:
MT-ND1
Uniprot ID:
P03886
Molecular Weight:
35660.055 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Target Details
8. Potassium voltage-gated channel subfamily A member 1
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:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729).
Gene Name:
KCNA1
Uniprot ID:
Q09470
Molecular Weight:
56465.01 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]