ARBUTAMINE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H23NO4
Molecular Weight	317.3795
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@@H](CNCCCCC1=CC=C(O)C=C1)C2=CC=C(O)C(O)=C2

InChI

InChIKey=IIRWWTKISYTTBL-SFHVURJKSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8723169 | https://www.glowm.com/resources/glowm/cd/pages/drugs/a056.html

Arbutamine was indicated to elicit acute cardiovascular responses in order to aid in diagnosing the presence or absence of coronary artery disease in patients who cannot exercise adequately. Arbutamine is a synthetic catecholamine with positive chronotropic and inotropic properties. The chronotropic (increase in heart rate [HR]) 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. 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 HR, cardiac contractility, and systolic blood pressure.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-1 adrenergic receptor 158 Target ID: P08588 Gene ID: 153.0 Gene Symbol: ADRB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8723169	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Coronary artery disease 48 Sources: https://www.glowm.com/resources/glowm/cd/pages/drugs/a056.html	Diagnostic		Approved 8429	GENESA Approved Use Unknown Launch Date 1997

T_1/2

Value	Dose	Co-administered	Analyte	Population
5 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020420ap-1.pdf	10 μg/kg single, intravenous dose: 10 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ARBUTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
42% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020420ap-1.pdf	10 μg/kg single, intravenous dose: 10 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ARBUTAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
4.62 mg/kg single, oral (mean) Recommended Dose: 4.62 mg/kg Route: oral Route: single Dose: 4.62 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 20-70 n = 53 Health Status: healthy Condition: diagnostic test Age Group: 20-70 Sex: M+F Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	Disc. AE: Arrhythmia, Hypotension... Other AEs: Arrhythmia... AEs leading to discontinuation/dose reduction: Arrhythmia (2%) Hypotension (9%) Other AEs: Arrhythmia (29 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	Disc. AE: Angina, Arrhythmia... Other AEs: Arrhythmia... AEs leading to discontinuation/dose reduction: Angina (21%) Arrhythmia (4%) Hypotension (4%) Dyspnea (4%) Other AEs: Arrhythmia (103 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/

AEs

AE	Significance	Dose	Population
Arrhythmia	2% Disc. AE	4.62 mg/kg single, oral (mean) Recommended Dose: 4.62 mg/kg Route: oral Route: single Dose: 4.62 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 20-70 n = 53 Health Status: healthy Condition: diagnostic test Age Group: 20-70 Sex: M+F Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	29 patients	4.62 mg/kg single, oral (mean) Recommended Dose: 4.62 mg/kg Route: oral Route: single Dose: 4.62 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 20-70 n = 53 Health Status: healthy Condition: diagnostic test Age Group: 20-70 Sex: M+F Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Hypotension	9% Disc. AE	4.62 mg/kg single, oral (mean) Recommended Dose: 4.62 mg/kg Route: oral Route: single Dose: 4.62 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 20-70 n = 53 Health Status: healthy Condition: diagnostic test Age Group: 20-70 Sex: M+F Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	103 patients	3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Angina	21% Disc. AE	3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	4% Disc. AE	3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Dyspnea	4% Disc. AE	3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Hypotension	4% Disc. AE	3.58 mg/kg single, oral (mean) Recommended Dose: 3.58 mg/kg Route: oral Route: single Dose: 3.58 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/	healthy, 37 - 79 years n = 134 Health Status: healthy Condition: diagnostic test Age Group: 37 - 79 years Sex: M+F Population Size: 134 Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	SULT1A1 29 SULT2A1 24

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
SULT1A1 29	substrate 3367 Sources: https://www.jbc.org/article/S0021-9258(20)55446-X/pdf#page=5 Page: 5.0	yes
SULT2A1 24	substrate 3367 Sources: https://www.jbc.org/article/S0021-9258(20)55446-X/pdf#page=5 Page: 5.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50580	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50580
MolPort	MolPort-006-167-706	https://www.molport.com/shop/molecule-link/MolPort-006-167-706

PubMed

Title	Date	PubMed
Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing.	1996 Mar	8723169
[Methodological aspects of performing exercise tests used in combination with perfusion scintigraphy of the myocardium].	2001	11494455
Identification of viable myocardium early after acute myocardial infarction using closed-loop arbutamine echocardiography: comparison with positron emission tomography.	2001 Dec	11791807
Pharmacological stress agents for evaluation of ischemic heart disease.	2001 Dec	11744132
Assessment of adenosine, arbutamine and dobutamine as pharmacological stress agents during (99m)Tc-tetrofosmin SPECT imaging: a randomized study.	2001 Dec	11711900
Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine.	2002 Aug 8	12153193
Arbutamine stress perfusion imaging in dogs with critical coronary artery stenoses: (99m)Tc-sestamibi versus (201)Tl.	2002 May	11994532
Pharmacologic interventions in nuclear radiology: indications, imaging protocols, and clinical results.	2002 May-Jun	12006682
Use of pharmaceuticals in noninvasive cardiovascular diagnosis.	2002 Sep-Oct	12350244
[Comparison of usefulness of dobutamine-atropine and dobutamine-adenosine stress echocardiography in detection of coronary artery disease].	2004 Apr	15517922
Myocardial perfusion scintigraphy: the evidence.	2004 Feb	15129710
Sonovue improves endocardial border detection and variability in assessing wall motion score and ejection fraction during stress echocardiography.	2004 Jan-Mar	15732229
Dobutamine stress echocardiography in healthy adult male rats.	2005 Oct 26	16250913
Asymmetric hydrogenation of alpha-primary and secondary amino ketones: efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine.	2007	17591728
Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography.	2007 Nov 21	18031577

Sample Use Guides

In Vivo Use Guide

Intravenous infusion, up to a maximum of 10 mcg per kg of body weight as administered by the drug delivery device

Route of Administration: Intravenous

In Vitro Use Guide

It was characterized the interactions of arbutamine with different adrenergic receptor subtypes in vitro. In the electrically stimulated left atria of rats, arbutamine increased contractile force. The pD2 values (- log of the dose that produces 50% of the maximal responses) for arbutamine and isoproterenol were 8.45 +/- 0.15 and 8.55 +/- 0.02, respectively. Both arbutamine and isoproterenol increased the rate of spontaneously beating rat right atria with pD2 values of 9.0 +/- 0.19 and 8.82 +/- 0.18, respectively. The affinity constants (KA) of arbutamine and isoproterenol for cardiac beta1-adrenergic receptors, as determined by competition binding assays, were found to be 7.32 and 6.04, respectively. In guinea pig trachea, arbutamine and isoproterenol produced a concentration-dependent relaxation that was blocked by propranolol. Their pD2 values were 7.9 +/- 0.1 and 8.2 +/- 0.1, respectively. Arbutamine contracted isolated rat aortic rings with a maximal increase of 38.1 +/- 6.7% that of 10 microM of norepinephrine. In rat white adipocytes, arbutamine, isoproterenol, and BRL-37344 stimulated glycerol release, with the order of potency being BRL-37344 > arbutamine > isoproterenol. In hamster brown adipocytes, the order was arbutamine > isoproterenol > BRL-37344. Moreover, arbutamine stimulated beta3-adrenergic receptors in guinea pig ileum. Arbutamine does not stimulate alpha-adrenergic receptors at concentrations that were high enough to maximally activate the beta-adrenergic receptors.

Name

Type

Language

ARBUTAMINE

Official Name

English

ARBUTAMINE [VANDF]

Common Name

English

ARBUTAMINE [MI]

Common Name

English

arbutamine [INN]

Common Name

English

Arbutamine [WHO-DD]

Common Name

English

1,2-BENZENEDIOL, 4-(1-HYDROXY-2-((4-(4-HYDROXYPHENYL)BUTYL)AMINO)ETHYL)-, (1R)

Common Name

English

(R)-3,4-DIHYDROXY-.ALPHA.-(((4-(P-HYDROXYPHENYL)BUTYL)AMINO)METHYL)BENZYL ALCOHOL

Common Name

English

Classification Tree Code System Code

WHO-ATC

C01CA22