Identification

Name
Arbutamine
Accession Number
DB01102  (APRD00802)
Type
Small Molecule
Groups
Approved
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
Synonyms
  • Arbutamina
  • Arbutaminum
Product Ingredients
IngredientUNIICASInChI Key
Arbutamine hydrochlorideK0NF2CPJ7F125251-66-3ATBUNPBAFFCFKY-FERBBOLQSA-N
International/Other Brands
GenESA
Categories
UNII
B07L15YAEV
CAS number
128470-16-6
Weight
Average: 317.3795
Monoisotopic: 317.162708229
Chemical Formula
C18H23NO4
InChI Key
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

Pharmacology

Indication

Used 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.

Pharmacodynamics
Not Available
Mechanism of action

Arbutamine 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.

TargetActionsOrganism
ABeta-1 adrenergic receptor
agonist
Human
UBeta-2 adrenergic receptor
agonist
Human
UBeta-3 adrenergic receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

58%

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.

Route of elimination
Not Available
Half life

Elimination half-life is approximately 8 minutes.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Arbutamine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Arbutamine.
AcebutololThe therapeutic efficacy of Arbutamine can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Arbutamine.
AlclometasoneThe risk or severity of hypokalemia can be increased when Alclometasone is combined with Arbutamine.
AlfuzosinThe therapeutic efficacy of Arbutamine can be decreased when used in combination with Alfuzosin.
AlprenololAlprenolol may decrease the bronchodilatory activities of Arbutamine.
AmcinonideThe risk or severity of hypokalemia can be increased when Amcinonide is combined with Arbutamine.
AmineptineThe risk or severity of adverse effects can be increased when Amineptine is combined with Arbutamine.
AmitriptylineThe therapeutic efficacy of Arbutamine can be decreased when used in combination with Amitriptyline.
AmitriptylinoxideThe risk or severity of adverse effects can be increased when Amitriptylinoxide is combined with Arbutamine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015234
PubChem Compound
60789
PubChem Substance
46509010
ChemSpider
54785
ChEBI
50580
ChEMBL
CHEMBL1201251
Therapeutic Targets Database
DAP000936
PharmGKB
PA164747979
Wikipedia
Arbutamine
ATC Codes
C01CA22 — Arbutamine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5395970No1995-03-072012-03-07Us
US5234404No1993-08-102010-08-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0842 mg/mLALOGPS
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 Area92.95 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity89.78 m3·mol-1ChemAxon
Polarizability35.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9464
Blood Brain Barrier-0.9026
Caco-2 permeable-0.7305
P-glycoprotein substrateSubstrate0.7596
P-glycoprotein inhibitor INon-inhibitor0.8011
P-glycoprotein inhibitor IINon-inhibitor0.5135
Renal organic cation transporterNon-inhibitor0.6511
CYP450 2C9 substrateNon-substrate0.8014
CYP450 2D6 substrateNon-substrate0.7951
CYP450 3A4 substrateNon-substrate0.5827
CYP450 1A2 substrateNon-inhibitor0.6669
CYP450 2C9 inhibitorNon-inhibitor0.9295
CYP450 2D6 inhibitorNon-inhibitor0.8282
CYP450 2C19 inhibitorNon-inhibitor0.9358
CYP450 3A4 inhibitorNon-inhibitor0.7648
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9401
Ames testNon AMES toxic0.7687
CarcinogenicityNon-carcinogens0.943
BiodegradationNot ready biodegradable0.5579
Rat acute toxicity1.9867 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6306
hERG inhibition (predictor II)Inhibitor0.7594
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylbutylamines
Direct Parent
Phenylbutylamines
Alternative Parents
Catechols / Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Phenylbutylamine / Catechol / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Aralkylamine / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
catecholamine (CHEBI:50580)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
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:17139284]
  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:17016423]
  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:8723169]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
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:8723169]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
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:8723169]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:39