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Identification
Name Alfentanil
Accession Number DB00802 (APRD00726)
Type small molecule
Groups illicit, approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Alfentanilum [INN-Latin]
Alfentanyl
Salts Not Available
Brand names
Name Company
Alfenta Taylor (United States)
Brand mixtures Not Available
Categories
  • Narcotics
  • Analgesics
  • Anesthetics
  • Anesthetics, Intravenous
  • Opiate Agonists
  • Analgesics, Opioid
CAS number 71195-58-9
Weight Average: 416.5172
Monoisotopic: 416.25358892
Chemical Formula C21H32N6O3
InChI Key InChIKey=IDBPHNDTYPBSNI-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Fentanyls
Substructures
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Acetanilides
  • Tetrazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Cyanamides
  • Anilines
  • Piperidines
  • Fentanyls
Pharmacology
Indication For the management of postoperative pain and the maintenance of general anesthesia.
Pharmacodynamics Alfentanil 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 action 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. 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.
Absorption For intravenous injection or infusion only.
Volume of distribution
  • 0.4 to 1 L/kg
Protein binding 92%
Metabolism The 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
Clearance
  • 5 mL/kg/min
Toxicity Symptoms 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
Pathway Name SMPDB ID
Smp00413 Alfentanil Pathway SMP00413
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Hospira inc
Packagers
Dosage forms
Form Route Strength
Injection, solution Intravenous 0.5 mg/ml
Prices
Unit description Cost Unit
Alfenta 500 mcg/ml ampul 5.26 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 140.8 °C PhysProp
water solubility 34.6 mg/L Not Available
logP 2.16 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 2.52e-01 g/l ALOGPS
logP 2.2 ALOGPS
logP 2.81 ChemAxon
logS -3.2 ALOGPS
pKa (strongest basic) 7.5 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 81.05 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 118.59 ChemAxon
polarizability 45.57 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C08005 Link_out
PubChem Compound 51263 Link_out
PubChem Substance 46505618 Link_out
ChemSpider 46451 Link_out
BindingDB 50008979 Link_out
ChEBI 2569 Link_out
ChEMBL 2569 Link_out
Therapeutic Targets Database DAP001134 Link_out
PharmGKB PA448084 Link_out
Drug Product Database 2248181 Link_out
RxList http://www.rxlist.com/cgi/generic2/alfent.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Alfentanil Link_out
ATC Codes
  • N01AH02
AHFS Codes
  • 28:08.08
PDB Entries Not Available
FDA label Not Available
MSDS show (51.3 KB)
Interactions
Drug Interactions
Drug Interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Cimetidine Increases the effect of the narcotic
Erythromycin The macrolide, erythromycin, may increase the effect and toxicity of alfentanil.
Fluconazole Increases the effect and toxicity of alfentanil
Itraconazole Itraconazole may increase the effect and toxicity of alfentanil.
Ketoconazole Ketoconazole may increase the effect and toxicity of alfentanil.
Rifampin Rifampin reduces levels and efficacy of alfentanil
Telithromycin Telithromycin 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.
Tranylcypromine Possible increased risk of serotonin syndrome.
Triprolidine The CNS depressants, Triprolidine and Alfentanil, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Voriconazole Voriconazole, 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 Interactions Not Available
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Carriers

1. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19