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Identification
NameArbutamine
Accession NumberDB01102  (APRD00802)
Typesmall molecule
Groupsapproved
Description

Arbutamine, administered through a closed-loop, computer-controlled drug-delivery system, is indicated to elicit acute cardiovascular responses, similar to those produced by exercise, in order to aid in diagnosing the presence or absence of coronary artery disease in patients who cannot exercise adequately .

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
GenESANot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number128470-16-6
WeightAverage: 317.3795
Monoisotopic: 317.162708229
Chemical FormulaC18H23NO4
InChI KeyInChIKey=IIRWWTKISYTTBL-SFHVURJKSA-N
InChI
InChI=1S/C18H23NO4/c20-15-7-4-13(5-8-15)3-1-2-10-19-12-18(23)14-6-9-16(21)17(22)11-14/h4-9,11,18-23H,1-3,10,12H2/t18-/m0/s1
IUPAC Name
4-[(1R)-1-hydroxy-2-{[4-(4-hydroxyphenyl)butyl]amino}ethyl]benzene-1,2-diol
SMILES
O[C@@H](CNCCCCC1=CC=C(O)C=C1)C1=CC(O)=C(O)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentCatecholamines and Derivatives
Alternative parentsSecondary Alcohols; Polyols; 1,2-Aminoalcohols; Enols; Dialkylamines; Polyamines
Substituents1,2-aminoalcohol; polyol; secondary alcohol; secondary aliphatic amine; polyamine; enol; secondary amine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the catecholamines and derivatives. These are compounds containing 4-(2-Aminoethyl)pyrocatechol [4-(2-aminoethyl)benzene-1,2-diol] or a derivative thereof formed by substitution.
Pharmacology
IndicationUsed to elicit acute cardiovascular responses (cardiac stumulant), similar to those produced by exercise, in order to aid in diagnosing the presence or absence of coronary artery disease (CAD) in patients who cannot exercise adequately.
PharmacodynamicsNot Available
Mechanism of actionArbutamine is a synthetic catecholamine with positive chronotropic and inotropic properties. The chronotropic (increase in heart rate) and inotropic (increase in force of contraction) effects of arbutamine serve to mimic exercise by increasing cardiac work (producing stress) and provoke myocardial ischemia in patients with compromised coronary arteries. The increase in heart rate caused by arbutamine is thought to limit regional subendocardial perfusion, thereby limiting tissue oxygenation. In functional assays, arbutamine is more selective for beta-adrenergic receptors than for alpha-adrenergic receptors. The beta-agonist activity of arbutamine provides cardiac stress by increasing heart rate, cardiac contractility, and systolic blood pressure. The degree of hypotension that occurs for a given chronotropic activity is less with arbutamine than, for example, with isoproterenol because alpha receptor activity is retained.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding58%
Metabolism

Primarily metabolized to methoxyarbutamine. Another possible metabolite is ketoarbutamine. The metabolites of arbutamine appear to have less pharmacological activity and a longer half-life and than the parental drug.

SubstrateEnzymesProduct
Arbutamine
    KetoarbutamineDetails
    Arbutamine
      MethoxyarbutamineDetails
      Route of eliminationNot Available
      Half lifeElimination half-life is approximately 8 minutes.
      ClearanceNot Available
      ToxicityNot Available
      Affected organisms
      • Humans and other mammals
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.9464
      Blood Brain Barrier - 0.9026
      Caco-2 permeable - 0.7305
      P-glycoprotein substrate Substrate 0.7596
      P-glycoprotein inhibitor I Non-inhibitor 0.8011
      P-glycoprotein inhibitor II Non-inhibitor 0.5135
      Renal organic cation transporter Non-inhibitor 0.6511
      CYP450 2C9 substrate Non-substrate 0.8014
      CYP450 2D6 substrate Non-substrate 0.7951
      CYP450 3A4 substrate Non-substrate 0.5827
      CYP450 1A2 substrate Non-inhibitor 0.6669
      CYP450 2C9 substrate Non-inhibitor 0.9295
      CYP450 2D6 substrate Non-inhibitor 0.8282
      CYP450 2C19 substrate Non-inhibitor 0.9358
      CYP450 3A4 substrate Non-inhibitor 0.7648
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9401
      Ames test Non AMES toxic 0.7687
      Carcinogenicity Non-carcinogens 0.943
      Biodegradation Not ready biodegradable 0.5579
      Rat acute toxicity 1.9867 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Strong inhibitor 0.6306
      hERG inhibition (predictor II) Inhibitor 0.7594
      Pharmacoeconomics
      Manufacturers
      • Gensia automedics inc
      PackagersNot Available
      Dosage formsNot Available
      PricesNot Available
      Patents
      CountryPatent NumberApprovedExpires (estimated)
      United States53959701995-03-072012-03-07
      United States52344041993-08-102010-08-10
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      logP2.9Not Available
      Predicted Properties
      PropertyValueSource
      water solubility8.42e-02 g/lALOGPS
      logP2.08ALOGPS
      logP2ChemAxon
      logS-3.6ALOGPS
      pKa (strongest acidic)8.97ChemAxon
      pKa (strongest basic)9.76ChemAxon
      physiological charge1ChemAxon
      hydrogen acceptor count5ChemAxon
      hydrogen donor count5ChemAxon
      polar surface area92.95ChemAxon
      rotatable bond count8ChemAxon
      refractivity89.78ChemAxon
      polarizability35.54ChemAxon
      number of rings2ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis ReferenceNot Available
      General ReferenceNot Available
      External Links
      ResourceLink
      PubChem Compound60789
      PubChem Substance46509010
      ChemSpider54785
      ChEBI50580
      ChEMBL
      Therapeutic Targets DatabaseDAP000936
      PharmGKBPA164747979
      ATC CodesC01CA22
      AHFS CodesNot Available
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSNot Available
      Interactions
      Drug InteractionsNot Available
      Food InteractionsNot Available

      1. Beta-1 adrenergic receptor

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: agonist

      Components

      Name UniProt ID Details
      Beta-1 adrenergic receptor P08588 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Abou-Mohamed G, Nagarajan R, Ibrahim TM, Caldwell RW: Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing. Cardiovasc Drugs Ther. 1996 Mar;10(1):39-47. Pubmed

      2. Beta-2 adrenergic receptor

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      Beta-2 adrenergic receptor P07550 Details

      References:

      1. Abou-Mohamed G, Nagarajan R, Ibrahim TM, Caldwell RW: Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing. Cardiovasc Drugs Ther. 1996 Mar;10(1):39-47. Pubmed

      3. Beta-3 adrenergic receptor

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      Beta-3 adrenergic receptor P13945 Details

      References:

      1. Abou-Mohamed G, Nagarajan R, Ibrahim TM, Caldwell RW: Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing. Cardiovasc Drugs Ther. 1996 Mar;10(1):39-47. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13