You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAlfentanil
Accession NumberDB00802  (APRD00726)
TypeSmall Molecule
GroupsApproved, Illicit
Description

A 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]

Structure
Thumb
Synonyms
SynonymLanguageCode
AlfentanilumLatinINN
AlfentanylNot AvailableNot Available
N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AlfentaTaylor (United States)
RapifenJanssen
Brand mixturesNot Available
Categories
CAS number71195-58-9
WeightAverage: 416.5172
Monoisotopic: 416.25358892
Chemical FormulaC21H32N6O3
InChI KeyIDBPHNDTYPBSNI-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
N-{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
SMILES
CCN1N=NN(CCN2CCC(COC)(CC2)N(C(=O)CC)C2=CC=CC=C2)C1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilides
Direct parentAnilides
Alternative parentsAminopiperidines; Tetrazoles; Tertiary Carboxylic Acid Amides; Tertiary Amines; Ethers; Enolates; Carboxylic Acids; Polyamines
Substituents4-aminopiperidine; piperidine; tetrazole; azole; tertiary carboxylic acid amide; tertiary amine; carboxamide group; carboxylic acid derivative; enolate; polyamine; carboxylic acid; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationFor the management of postoperative pain and the maintenance of general anesthesia.
PharmacodynamicsAlfentanil is a synthetic opioid analgesic. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.
Mechanism of actionOpiate 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.
AbsorptionFor intravenous injection or infusion only.
Volume of distribution
  • 0.4 to 1 L/kg
Protein binding92%
Metabolism

The liver is the major site of biotransformation.

SubstrateEnzymesProduct
Alfentanil
AMXDetails
Alfentanil
noralfentanilDetails
Route of eliminationOnly 1.0% of the dose is excreted as unchanged drug; urinary excretion is the major route of elimination of metabolites.
Half life90-111 minutes
Clearance
  • 5 mL/kg/min
ToxicitySymptoms of overexposure include characteristic rigidity of the skeletal muscles, cardiac and respiratory depression, and narrowing of the pupils.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Alfentanil Action PathwayDrug actionSMP00413
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9957
Blood Brain Barrier + 0.9396
Caco-2 permeable - 0.5368
P-glycoprotein substrate Substrate 0.7156
P-glycoprotein inhibitor I Inhibitor 0.8809
P-glycoprotein inhibitor II Non-inhibitor 0.8381
Renal organic cation transporter Non-inhibitor 0.7077
CYP450 2C9 substrate Non-substrate 0.7897
CYP450 2D6 substrate Non-substrate 0.9115
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.9067
CYP450 2C9 substrate Inhibitor 0.6051
CYP450 2D6 substrate Non-inhibitor 0.9003
CYP450 2C19 substrate Non-inhibitor 0.5591
CYP450 3A4 substrate Inhibitor 0.6691
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6692
Ames test AMES toxic 0.5858
Carcinogenicity Non-carcinogens 0.7729
Biodegradation Not ready biodegradable 0.9877
Rat acute toxicity 2.9997 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.6413
hERG inhibition (predictor II) Inhibitor 0.5893
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous0.5 mg/ml
Prices
Unit descriptionCostUnit
Alfenta 500 mcg/ml ampul5.26USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point140.8Janssens, F.; US. Patent 4,167,574; September 11, 1979; assigned to Janssen Pharmaceutica NV.
water solubility34.6 mg/LNot Available
logP2.16HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.252ALOGPS
logP2.2ALOGPS
logP2.81ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)7.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area81.05 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity118.59 m3·mol-1ChemAxon
Polarizability45.57 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
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.

US20060149071
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC08005
PubChem Compound51263
PubChem Substance46505618
ChemSpider46451
BindingDB50008979
ChEBI2569
ChEMBLCHEMBL634
Therapeutic Targets DatabaseDAP001134
PharmGKBPA448084
Drug Product Database2248181
RxListhttp://www.rxlist.com/cgi/generic2/alfent.htm
WikipediaAlfentanil
ATC CodesN01AH02
AHFS Codes
  • 28:08.08
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(51.3 KB)
Interactions
Drug Interactions
Drug
AlvimopanIncreases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
CimetidineIncreases the effect of the narcotic
ErythromycinThe macrolide, erythromycin, may increase the effect and toxicity of alfentanil.
FluconazoleIncreases the effect and toxicity of alfentanil
ItraconazoleItraconazole may increase the effect and toxicity of alfentanil.
KetoconazoleKetoconazole may increase the effect and toxicity of alfentanil.
RifampicinRifampin reduces levels and efficacy of alfentanil
TelithromycinTelithromycin may reduce clearance of Alfentanil. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Alfentanil if Telithromycin is initiated, discontinued or dose changed.
TranylcyprominePossible increased risk of serotonin syndrome.
TriprolidineThe CNS depressants, Triprolidine and Alfentanil, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of alfentanil by decreasing its metabolism. Monitor for increased anesthetic and respiratory depressant effects and consider using lower alfentanil doses or alternate anesthetic.
Food InteractionsNot Available

Targets

1. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

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. Pubmed
  2. Lotsch J, Geisslinger G: Are mu-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol Med. 2005 Feb;11(2):82-9. Pubmed
  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. Pubmed
  4. Leung A, Wallace MS, Ridgeway B, Yaksh T: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. 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. Pubmed

2. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

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. Pubmed
  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. Pubmed

2. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

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. Pubmed
  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. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12