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.

Structured Indications
Not Available
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
DrugInteractionDrug group
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.Experimental
AcebutololAcebutolol may decrease the bronchodilatory activities of Arbutamine.Approved
AlfuzosinAlfuzosin may decrease the vasoconstricting activities of Arbutamine.Approved, Investigational
AlprenololAlprenolol may decrease the bronchodilatory activities of Arbutamine.Approved, Withdrawn
AmineptineThe risk or severity of adverse effects can be increased when Amineptine is combined with Arbutamine.Illicit, Withdrawn
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Arbutamine.Approved
AtenololAtenolol may decrease the bronchodilatory activities of Arbutamine.Approved
AtomoxetineAtomoxetine may increase the tachycardic activities of Arbutamine.Approved
AtosibanThe risk or severity of adverse effects can be increased when Arbutamine is combined with Atosiban.Approved
BendroflumethiazideArbutamine may increase the hypokalemic activities of Bendroflumethiazide.Approved
BenmoxinThe risk or severity of adverse effects can be increased when Benmoxin is combined with Arbutamine.Withdrawn
Benzylpenicilloyl PolylysineArbutamine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Arbutamine can be decreased when used in combination with Betahistine.Approved
BetaxololBetaxolol may decrease the bronchodilatory activities of Arbutamine.Approved
BisoprololBisoprolol may decrease the bronchodilatory activities of Arbutamine.Approved
BopindololBopindolol may decrease the bronchodilatory activities of Arbutamine.Approved
BrofaromineThe risk or severity of adverse effects can be increased when Brofaromine is combined with Arbutamine.Experimental
BromocriptineBromocriptine may increase the hypertensive activities of Arbutamine.Approved, Investigational
BucindololBucindolol may decrease the vasoconstricting activities of Arbutamine.Investigational
BumetanideArbutamine may increase the hypokalemic activities of Bumetanide.Approved
BunazosinBunazosin may decrease the vasoconstricting activities of Arbutamine.Investigational
BupranololBupranolol may decrease the bronchodilatory activities of Arbutamine.Approved
CabergolineCabergoline may increase the hypertensive activities of Arbutamine.Approved
CaroxazoneThe risk or severity of adverse effects can be increased when Caroxazone is combined with Arbutamine.Withdrawn
CarteololCarteolol may decrease the bronchodilatory activities of Arbutamine.Approved
CarvedilolCarvedilol may decrease the vasoconstricting activities of Arbutamine.Approved, Investigational
CeliprololCeliprolol may decrease the bronchodilatory activities of Arbutamine.Approved, Investigational
ChlorothiazideArbutamine may increase the hypokalemic activities of Chlorothiazide.Approved, Vet Approved
ChlorthalidoneArbutamine may increase the hypokalemic activities of Chlorthalidone.Approved
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Arbutamine.Approved, Vet Approved
CloranololCloranolol may decrease the bronchodilatory activities of Arbutamine.Experimental
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Arbutamine.Approved
CyclopenthiazideArbutamine may increase the hypokalemic activities of Cyclopenthiazide.Experimental
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Arbutamine.Approved
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Arbutamine.Approved
DibenzepinThe risk or severity of adverse effects can be increased when Dibenzepin is combined with Arbutamine.Experimental
DihydroergotamineDihydroergotamine may increase the hypertensive activities of Arbutamine.Approved
DosulepinThe risk or severity of adverse effects can be increased when Dosulepin is combined with Arbutamine.Approved
DoxazosinDoxazosin may decrease the vasoconstricting activities of Arbutamine.Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Arbutamine.Approved
DuloxetineDuloxetine may increase the tachycardic activities of Arbutamine.Approved
Ergoloid mesylateErgoloid mesylate may increase the hypertensive activities of Arbutamine.Approved
ErgonovineErgonovine may increase the hypertensive activities of Arbutamine.Approved
ErgotamineErgotamine may increase the hypertensive activities of Arbutamine.Approved
EsmirtazapineThe risk or severity of adverse effects can be increased when Esmirtazapine is combined with Arbutamine.Investigational
EsmololEsmolol may decrease the bronchodilatory activities of Arbutamine.Approved
Etacrynic acidArbutamine may increase the hypokalemic activities of Etacrynic acid.Approved
FurazolidoneThe risk or severity of adverse effects can be increased when Furazolidone is combined with Arbutamine.Approved, Vet Approved
FurosemideArbutamine may increase the hypokalemic activities of Furosemide.Approved, Vet Approved
HarmalineThe risk or severity of adverse effects can be increased when Harmaline is combined with Arbutamine.Experimental
HydracarbazineThe risk or severity of adverse effects can be increased when Hydracarbazine is combined with Arbutamine.Experimental
HydrochlorothiazideArbutamine may increase the hypokalemic activities of Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideArbutamine may increase the hypokalemic activities of Hydroflumethiazide.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Arbutamine.Approved
IndapamideArbutamine may increase the hypokalemic activities of Indapamide.Approved
IndoraminIndoramin may decrease the vasoconstricting activities of Arbutamine.Withdrawn
IprindoleThe risk or severity of adverse effects can be increased when Iprindole is combined with Arbutamine.Experimental
IproclozideThe risk or severity of adverse effects can be increased when Iproclozide is combined with Arbutamine.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Iproniazid is combined with Arbutamine.Withdrawn
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Arbutamine.Approved
LabetalolLabetalol may decrease the vasoconstricting activities of Arbutamine.Approved
LevomilnacipranLevomilnacipran may increase the tachycardic activities of Arbutamine.Approved
LofepramineThe risk or severity of adverse effects can be increased when Lofepramine is combined with Arbutamine.Experimental
MebanazineThe risk or severity of adverse effects can be increased when Mebanazine is combined with Arbutamine.Withdrawn
MepindololMepindolol may decrease the bronchodilatory activities of Arbutamine.Experimental
MethyclothiazideArbutamine may increase the hypokalemic activities of Methyclothiazide.Approved
Methylene blueThe risk or severity of adverse effects can be increased when Methylene blue is combined with Arbutamine.Investigational
MethylergometrineMethylergometrine may increase the hypertensive activities of Arbutamine.Approved
MetolazoneArbutamine may increase the hypokalemic activities of Metolazone.Approved
MetoprololMetoprolol may decrease the bronchodilatory activities of Arbutamine.Approved, Investigational
MilnacipranMilnacipran may increase the tachycardic activities of Arbutamine.Approved
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Arbutamine.Approved
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Arbutamine.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Arbutamine.Approved
NebivololNebivolol may decrease the bronchodilatory activities of Arbutamine.Approved, Investigational
NialamideThe risk or severity of adverse effects can be increased when Nialamide is combined with Arbutamine.Withdrawn
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Arbutamine.Approved
OctamoxinThe risk or severity of adverse effects can be increased when Octamoxin is combined with Arbutamine.Withdrawn
OpipramolThe risk or severity of adverse effects can be increased when Opipramol is combined with Arbutamine.Investigational
OxprenololOxprenolol may decrease the bronchodilatory activities of Arbutamine.Approved
PargylineThe risk or severity of adverse effects can be increased when Pargyline is combined with Arbutamine.Approved
PenbutololPenbutolol may decrease the bronchodilatory activities of Arbutamine.Approved, Investigational
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Arbutamine.Approved
PheniprazineThe risk or severity of adverse effects can be increased when Pheniprazine is combined with Arbutamine.Withdrawn
PhenoxypropazineThe risk or severity of adverse effects can be increased when Phenoxypropazine is combined with Arbutamine.Withdrawn
PiretanideArbutamine may increase the hypokalemic activities of Piretanide.Experimental
PirlindoleThe risk or severity of adverse effects can be increased when Pirlindole is combined with Arbutamine.Approved
PivhydrazineThe risk or severity of adverse effects can be increased when Pivhydrazine is combined with Arbutamine.Withdrawn
PolythiazideArbutamine may increase the hypokalemic activities of Polythiazide.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Arbutamine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Arbutamine.Approved
QuinethazoneArbutamine may increase the hypokalemic activities of Quinethazone.Approved
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Arbutamine.Approved
SafrazineThe risk or severity of adverse effects can be increased when Safrazine is combined with Arbutamine.Withdrawn
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Arbutamine.Approved, Investigational, Vet Approved
SilodosinSilodosin may decrease the vasoconstricting activities of Arbutamine.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Arbutamine.Approved
TamsulosinTamsulosin may decrease the vasoconstricting activities of Arbutamine.Approved, Investigational
TerazosinTerazosin may decrease the vasoconstricting activities of Arbutamine.Approved
TertatololTertatolol may decrease the bronchodilatory activities of Arbutamine.Experimental
TianeptineThe risk or severity of adverse effects can be increased when Tianeptine is combined with Arbutamine.Approved
TimololTimolol may decrease the bronchodilatory activities of Arbutamine.Approved
ToloxatoneThe risk or severity of adverse effects can be increased when Toloxatone is combined with Arbutamine.Approved
TorasemideArbutamine may increase the hypokalemic activities of Torasemide.Approved
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Arbutamine.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Arbutamine.Approved
TrichlormethiazideArbutamine may increase the hypokalemic activities of Trichlormethiazide.Approved, Vet Approved
TrimazosinTrimazosin may decrease the vasoconstricting activities of Arbutamine.Experimental
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Arbutamine.Approved
UrapidilUrapidil may decrease the vasoconstricting activities of Arbutamine.Investigational
VenlafaxineVenlafaxine may increase the tachycardic activities of Arbutamine.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
Human Metabolome Database
HMDB15234
PubChem Compound
60789
PubChem Substance
46509010
ChemSpider
54785
ChEBI
50580
ChEMBL
CHEMBL1201251
Therapeutic Targets Database
DAP000936
PharmGKB
PA164747979
ATC Codes
C01CA22 — Arbutamine
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

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 02, 2017 04:52