Alfentanil (T3D2894)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2009-07-21 20:27:40 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2894
Identification
Common NameAlfentanil
ClassSmall Molecule
DescriptionA short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients. [PubChem]
Compound Type
  • Amide
  • Amine
  • Analgesic
  • Analgesic, Opioid
  • Anesthetic
  • Anesthetic, Intravenous
  • Drug
  • Ether
  • Metabolite
  • Narcotic
  • Opiate Agonist
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Alfenta
Alfentanilum
Alfentanyl
N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide
Rapifen
Chemical FormulaC21H32N6O3
Average Molecular Mass416.517 g/mol
Monoisotopic Mass416.254 g/mol
CAS Registry Number71195-58-9
IUPAC NameN-{1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-1,2,3,4-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl}-N-phenylpropanamide
Traditional Namealfentanil
SMILESCCN1N=NN(CCN2CCC(COC)(CC2)N(C(=O)CC)C2=CC=CC=C2)C1=O
InChI IdentifierInChI=1S/C21H32N6O3/c1-4-19(28)27(18-9-7-6-8-10-18)21(17-30-3)11-13-24(14-12-21)15-16-26-20(29)25(5-2)22-23-26/h6-10H,4-5,11-17H2,1-3H3
InChI KeyInChIKey=IDBPHNDTYPBSNI-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
  • Piperidine
  • Azole
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Tetrazole
  • Amino acid or derivatives
  • Carboxamide group
  • Tertiary amine
  • Tertiary aliphatic amine
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organopnictogen compound
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point140.8°C
Boiling PointNot Available
Solubility34.6 mg/L
LogP2.16
Predicted Properties
PropertyValueSource
Water Solubility0.25 g/LALOGPS
logP2.2ALOGPS
logP2.81ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)7.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area81.05 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity118.59 m³·mol⁻¹ChemAxon
Polarizability45.57 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-0aps-5759000000-11ce8f647981a86e29932017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0000900000-a802cc961dad7c6326a52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0395300000-498fafc6962b6fd82e9c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00kb-0912000000-43c2343a5fa4997ca93a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-015a-2900000000-16b845b2c742175e38cd2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-015a-7900000000-e9bd243460dd405076192017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-015a-2900000000-16b845b2c742175e38cd2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-015a-7900000000-e9bd243460dd405076192021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00kb-0912000000-43c2343a5fa4997ca93a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00kb-0912000000-b5e89d86b302adb655172021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-015a-2900000000-d76f968c16c60e097fbc2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-014i-0395300000-498fafc6962b6fd82e9c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014i-0000900000-a802cc961dad7c6326a52021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-015a-7900000000-7fdf62ef447e7c6e19fa2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00kb-0912000000-1f6c2333f39ce390e20e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-015a-7900000000-1c558c3f776664f15eb12021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-9007000000-cbc10f94b61327a4ec792016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9022000000-5dee7e8e9ca18ed6afa72016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9052000000-d1f0fa6385e6848912c62016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0cdr-6509300000-1d06eb64c3c9a376ea432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-3109000000-3960d2bbff65d1a0ecc02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0btc-9423000000-8194ccf6d27ec2cb28702016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0000900000-1e0b9eadc3dc511d87d72021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0392100000-333cd54e08c49ae75cde2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0296-1936000000-2f1acf618b9904cbaffe2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009300000-f5e9f9e4f40759f2ff432021-10-11View Spectrum
Toxicity Profile
Route of ExposureFor intravenous injection or infusion only.
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. Alfentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
MetabolismThe liver is the major site of biotransformation. Route of Elimination: Only 1.0% of the dose is excreted as unchanged drug; urinary excretion is the major route of elimination of metabolites. Half Life: 90-111 minutes
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the management of postoperative pain and the maintenance of general anesthesia.
Minimum Risk LevelNot Available
Health EffectsMedical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
SymptomsSymptoms of overexposure include characteristic rigidity of the skeletal muscles, cardiac and respiratory depression, and narrowing of the pupils.
TreatmentIntravenous administration of an opioid antagonist such as naloxone should be employed as a specific antidote to manage respiratory depression. The duration of respiratory depression following overdosage with ALFENTA may be longer than the duration of action of the opioid antagonist. Administration of an opioid antagonist should not preclude immediate establishment of a patent airway, administration of oxygen, and assisted or controlled ventilation as indicated for hypoventilation or apnea. If respiratory depression is associated with muscular rigidity, a neuromuscular blocking agent may be required to facilitate assisted or controlled ventilation. Intravenous fluids and vasoactive agents may be required to manage hemodynamic instability. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00802
HMDB IDHMDB14940
PubChem Compound ID51263
ChEMBL IDCHEMBL634
ChemSpider ID46451
KEGG IDC08005
UniProt IDNot Available
OMIM ID
ChEBI ID2569
BioCyc IDNot Available
CTD IDNot Available
Stitch IDAlfentanil
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAlfentanil
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]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Mu-type opioid receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.015 uMNot AvailableBindingDB 50008979
References
  1. Garrido M, Gubbens-Stibbe J, Tukker E, Cox E, von Frijtag J, Kunzel D, IJzerman A, Danhof M, van der Graaf PH: Pharmacokinetic-pharmacodynamic analysis of the EEG effect of alfentanil in rats following beta-funaltrexamine-induced mu-opioid receptor "knockdown" in vivo. Pharm Res. 2000 Jun;17(6):653-9. [10955836 ]
  2. Lotsch J, Geisslinger G: Are mu-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol Med. 2005 Feb;11(2):82-9. [15694871 ]
  3. Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lotsch J: The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics. 2006 Sep;16(9):625-36. [16906017 ]
  4. Bagley JR, Thomas SA, Rudo FG, Spencer HK, Doorley BM, Ossipov MH, Jerussi TP, Benvenga MJ, Spaulding T: New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics. J Med Chem. 1991 Feb;34(2):827-41. [1847432 ]
Target Details
2. Alpha-1-acid glycoprotein 1
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. Belpaire FM, Bogaert MG: Binding of alfentanil to human alpha 1-acid glycoprotein, albumin and serum. Int J Clin Pharmacol Ther Toxicol. 1991 Mar;29(3):96-102. [2071261 ]
  2. Gepts E, Heytens L, Camu F: Pharmacokinetics and placental transfer of intravenous and epidural alfentanil in parturient women. Anesth Analg. 1986 Nov;65(11):1155-60. [2876662 ]
  3. Kumar K, Crankshaw DP, Morgan DJ, Beemer GH: The effect of cardiopulmonary bypass on plasma protein binding of alfentanil. Eur J Clin Pharmacol. 1988;35(1):47-52. [3146505 ]
Target Details
3. Cytochrome P450 3A5
General Function:
Oxygen binding
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Klees TM, Sheffels P, Dale O, Kharasch ED: Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes. Drug Metab Dispos. 2005 Mar;33(3):303-11. Epub 2004 Nov 22. [15557344 ]
  2. Klees TM, Sheffels P, Thummel KE, Kharasch ED: Pharmacogenetic determinants of human liver microsomal alfentanil metabolism and the role of cytochrome P450 3A5. Anesthesiology. 2005 Mar;102(3):550-6. [15731592 ]
  3. Kharasch ED, Walker A, Isoherranen N, Hoffer C, Sheffels P, Thummel K, Whittington D, Ensign D: Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam. Clin Pharmacol Ther. 2007 Oct;82(4):410-26. Epub 2007 Jun 6. [17554244 ]
Target Details
4. Serum albumin
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Belpaire FM, Bogaert MG: Binding of alfentanil to human alpha 1-acid glycoprotein, albumin and serum. Int J Clin Pharmacol Ther Toxicol. 1991 Mar;29(3):96-102. [2071261 ]
  2. Kumar K, Crankshaw DP, Morgan DJ, Beemer GH: The effect of cardiopulmonary bypass on plasma protein binding of alfentanil. Eur J Clin Pharmacol. 1988;35(1):47-52. [3146505 ]
  3. Bower S, Sear JW: Disposition of alfentanil in patients receiving a renal transplant. J Pharm Pharmacol. 1989 Sep;41(9):654-7. [2573716 ]
Target Details
5. Multidrug resistance protein 1
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
IC50112 uMNot AvailableBindingDB 50008979
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 ]
  2. Kalvass JC, Olson ER, Pollack GM: Pharmacokinetics and pharmacodynamics of alfentanil in P-glycoprotein-competent and P-glycoprotein-deficient mice: P-glycoprotein efflux alters alfentanil brain disposition and antinociception. Drug Metab Dispos. 2007 Mar;35(3):455-9. Epub 2006 Dec 18. [17178769 ]
Target Details
6. Kappa-type opioid receptor
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
IC50>10 uMNot AvailableBindingDB 50008979
References
  1. Bagley JR, Thomas SA, Rudo FG, Spencer HK, Doorley BM, Ossipov MH, Jerussi TP, Benvenga MJ, Spaulding T: New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics. J Med Chem. 1991 Feb;34(2):827-41. [1847432 ]