ARBUTAMINE HYDROCHLORIDE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H23NO4.ClH
Molecular Weight	353.84
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=ATBUNPBAFFCFKY-FERBBOLQSA-N

InChI=1S/C18H23NO4.ClH/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;1H/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 163 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 2752

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 8583	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 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 Health Status: healthy Age Group: 20-70 Sex: M+F 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 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F 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 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 Health Status: healthy Age Group: 20-70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	29 patients	4.62 mg/kg single, oral 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 Health Status: healthy Age Group: 20-70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Hypotension	9% Disc. AE	4.62 mg/kg single, oral 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 Health Status: healthy Age Group: 20-70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	103 patients	3.58 mg/kg single, oral 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Angina	21% Disc. AE	3.58 mg/kg single, oral 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Arrhythmia	4% Disc. AE	3.58 mg/kg single, oral 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Dyspnea	4% Disc. AE	3.58 mg/kg single, oral 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/
Hypotension	4% Disc. AE	3.58 mg/kg single, oral 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 Health Status: healthy Age Group: 37 - 79 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7594028/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	SULT1A1 37 SULT2A1 28

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
SULT1A1 37	substrate 4014 Sources: https://www.jbc.org/article/S0021-9258(20)55446-X/pdf#page=5 Page: 5.0	yes
SULT2A1 28	substrate 4014 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
Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography.	2007-11-21	18031577
Asymmetric hydrogenation of alpha-primary and secondary amino ketones: efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine.	2007	17591728
Dobutamine stress echocardiography in healthy adult male rats.	2005-10-26	16250913
Sonovue improves endocardial border detection and variability in assessing wall motion score and ejection fraction during stress echocardiography.	2005-03-01	15732229
[Comparison of usefulness of dobutamine-atropine and dobutamine-adenosine stress echocardiography in detection of coronary artery disease].	2004-04	15517922
Myocardial perfusion scintigraphy: the evidence.	2004-02	15129710
Use of pharmaceuticals in noninvasive cardiovascular diagnosis.	2002-09-28	12350244
Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine.	2002-08-08	12153193
Pharmacologic interventions in nuclear radiology: indications, imaging protocols, and clinical results.	2002-05-15	12006682
Arbutamine stress perfusion imaging in dogs with critical coronary artery stenoses: (99m)Tc-sestamibi versus (201)Tl.	2002-05	11994532
Identification of viable myocardium early after acute myocardial infarction using closed-loop arbutamine echocardiography: comparison with positron emission tomography.	2001-12	11791807
Pharmacological stress agents for evaluation of ischemic heart disease.	2001-12	11744132
Assessment of adenosine, arbutamine and dobutamine as pharmacological stress agents during (99m)Tc-tetrofosmin SPECT imaging: a randomized study.	2001-12	11711900
Incremental prognostic value of RNA ejection fraction measurements during pharmacologic stress testing: a comparison with clinical and perfusion variables.	2001-06	11390550
Arbutamine stimulation detects viable myocardium 4 weeks after coronary occlusion.	2001-02	11174448
[Methodological aspects of performing exercise tests used in combination with perfusion scintigraphy of the myocardium].	2001	11494455
Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing.	1996-03	8723169

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

GENESA

Preferred Name

English

ARBUTAMINE HYDROCHLORIDE

Official Name

English

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

Common Name

English

GP-2-121-3

Code

English

ARBUTAMINE HYDROCHLORIDE [MART.]

Common Name

English

Arbutamine hydrochloride [WHO-DD]

Common Name

English

ARBUTAMINE HYDROCHLORIDE [USAN]

Common Name

English

ARBUTAMINE HCL

Common Name

English

ARBUTAMINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

ARBUTAMINE HYDROCHLORIDE [MI]

Common Name

English

ARBUTAMINE HYDROCHLORIDE [VANDF]

Common Name

English

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

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C48149