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Record Information
Version2.0
Creation Date2009-07-21 20:27:27 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2865
Identification
Common NameSufentanil
ClassSmall Molecule
DescriptionSufentanil is only found in individuals that have used or taken this drug. It is an opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. [PubChem]Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Sufentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids open calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
Compound Type
  • Adjuvant, Anesthesia
  • Amide
  • Amine
  • Analgesic, Opioid
  • Anesthetic, Intravenous
  • Drug
  • Ether
  • Metabolite
  • Narcotic
  • Opiate Agonist
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Chronogesic
Disufen
Fastfen
N-(4-(Methoxymethyl)-1-(2-(2-thienyl)ethyl)-4-piperidinyl)-N-phenylpropanamide
N-(4-(Methoxymethyl)-1-(2-(2-thienyl)ethyl)-4-piperidyl)propionanilide
Sufenta
Sufenta Forte
Sufenta mite
Sufentanil Citrate
Sufentanilo
Sufentanilum
Sufentanyl
Sufentil
Zuftil
Chemical FormulaC22H30N2O2S
Average Molecular Mass386.551 g/mol
Monoisotopic Mass386.203 g/mol
CAS Registry Number56030-54-7
IUPAC NameN-[4-(methoxymethyl)-1-[2-(thiophen-2-yl)ethyl]piperidin-4-yl]-N-phenylpropanamide
Traditional Namesufentanil
SMILESCCC(=O)N(C1=CC=CC=C1)C1(COC)CCN(CCC2=CC=CS2)CC1
InChI IdentifierInChI=1S/C22H30N2O2S/c1-3-21(25)24(19-8-5-4-6-9-19)22(18-26-2)12-15-23(16-13-22)14-11-20-10-7-17-27-20/h4-10,17H,3,11-16,18H2,1-2H3
InChI KeyInChIKey=GGCSSNBKKAUURC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilides
Direct ParentAnilides
Alternative Parents
Substituents
  • Anilide
  • Aralkylamine
  • Piperidine
  • Tertiary carboxylic acid amide
  • Heteroaromatic compound
  • Thiophene
  • Amino acid or derivatives
  • Carboxamide group
  • Tertiary amine
  • Tertiary aliphatic amine
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Sufentanil PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point97°C
Boiling PointNot Available
Solubility76 mg/L (at 25°C)
LogP3.95
Predicted Properties
PropertyValueSource
Water Solubility0.012 g/LALOGPS
logP3.4ALOGPS
logP3.61ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.86ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.78 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity111.42 m³·mol⁻¹ChemAxon
Polarizability43.85 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0019-5492000000-9d94c514876bdc8387e0JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0009000000-0f9e477eb2153eb20409JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0096000000-73641c83c08b872641cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-06ri-1981000000-b5f4aaab095cc6fc533cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-1900000000-2fdfd1d5fa6e43fa1604JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-4900000000-bd92c052347dc0822a01JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-06ri-1981000000-b5f4aaab095cc6fc533cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-06ri-1981000000-21ca95f5c20b4e4d757bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03di-1900000000-9e39677aeb59104a8067JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03di-1900000000-2fdfd1d5fa6e43fa1604JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-000i-0096000000-73641c83c08b872641cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-0f9e477eb2153eb20409JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-06ri-1981000000-e1ff77f1523c87ecb91fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03di-1900000000-60ef0f8a9d7e876ae46dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-03di-4900000000-48241c15de4549023508JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-03di-4900000000-bd92c052347dc0822a01JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-c5724e75fd2eba4a33acJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0bta-4598000000-80bef262238fe0a2f79eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0909-6691000000-402460d2376f94ba18b6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1009000000-0cb97625e6c980ac5389JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-054t-1149000000-17778ea8e91b31088014JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0aor-9281000000-2236691fcff93ab6da35JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0019000000-f5e780ad77af70f3877fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0598000000-624e87a85c6af29ccc41JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03du-1982000000-21b1cb138ec2a44e332dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0009000000-b423e34763d99ec623ffJSpectraViewer
Toxicity Profile
Route of ExposureEpidural; parenteral(intravenous)
Mechanism of ToxicityOpiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Sufentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids open calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
Metabolism Half Life: 265 minutes
Toxicity ValuesLD50: 18.7 mg/kg (parenteral-intravenous, mouse)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThe main use of this medication is in operating suites and critical care where pain relief is required for a short period of time. It also offers properties of sedation and this makes it a good analgesic component of anaesthetic regimen during an operation. [Wikipedia]. Also used as an analgesic adjunct in anesthesia and as a primary anesthetic drug in procedures requiring assisted ventilation and in the relief of pain.
Minimum Risk LevelNot Available
Health Effectsmay cause respiratory arrest. [Wikipedia] Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
SymptomsRespiratory depression. [Wikipedia]
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00708
HMDB IDHMDB14846
PubChem Compound ID41693
ChEMBL IDCHEMBL658
ChemSpider ID38043
KEGG IDC08022
UniProt IDNot Available
OMIM ID
ChEBI ID9316
BioCyc IDNot Available
CTD IDNot Available
Stitch IDSufentanil
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkSufentanil
References
Synthesis Reference

Jacob Mathew, J. Killgore, “New methods for the synthesis of alfentanil, sufentanil, and remifentanil.” U.S. Patent US20060149071, issued July 06, 2006.

MSDSLink
General References
  1. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Hurle MA: Changes in the expression of G protein-coupled receptor kinases and beta-arrestin 2 in rat brain during opioid tolerance and supersensitivity. J Neurochem. 2001 Apr;77(2):486-92. [11299311 ]
  3. Levron JC: [Pharmacokinetics and pharmacodynamics of morphinomimetics in the central nervous system]. Agressologie. 1991;32(6-7):318-20. [1688220 ]
  4. Ilien B, Galzi JL, Mejean A, Goeldner M, Hirth C: A mu-opioid receptor-filter assay. Rapid estimation of binding affinity of ligands and reversibility of long-lasting ligand-receptor complexes. Biochem Pharmacol. 1988 Oct 15;37(20):3843-51. [2847746 ]
  5. Colpaert FC, Leysen JE, Michiels M, van den Hoogen RH: Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain. Anesthesiology. 1986 Jul;65(1):41-9. [3014923 ]
  6. Leysen JE, Gommeren W: In vitro binding properties of 3H-sufentanil, a superior ligand for the mu-opiate receptor. Arch Int Pharmacodyn Ther. 1982 Dec;260(2):287-9. [6131653 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.05 uMNot AvailableBindingDB 50012490
References
  1. Freye E, Latasch L, Portoghese PS: The delta receptor is involved in sufentanil-induced respiratory depression--opioid subreceptors mediate different effects. Eur J Anaesthesiol. 1992 Nov;9(6):457-62. [1330549 ]
  2. Zhu J, Xue JC, Law PY, Claude PA, Luo LY, Yin J, Chen C, Liu-Chen LY: The region in the mu opioid receptor conferring selectivity for sufentanil over the delta receptor is different from that over the kappa receptor. FEBS Lett. 1996 Apr 15;384(2):198-202. [8612823 ]
  3. Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T: Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4. [8114680 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.075 uMNot AvailableBindingDB 50012490
References
  1. Zhu J, Xue JC, Law PY, Claude PA, Luo LY, Yin J, Chen C, Liu-Chen LY: The region in the mu opioid receptor conferring selectivity for sufentanil over the delta receptor is different from that over the kappa receptor. FEBS Lett. 1996 Apr 15;384(2):198-202. [8612823 ]
  2. Chang HM, Berde CB, Holz GG 4th, Steward GF, Kream RM: Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions. Anesthesiology. 1989 Apr;70(4):672-7. [2467589 ]
  3. Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T: Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4. [8114680 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC504.5 uMNot AvailableBindingDB 50012490
References
  1. Wandel C, Kim R, Wood M, Wood A: Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology. 2002 Apr;96(4):913-20. [11964599 ]