BUPRANOLOL HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H22ClNO2.ClH
Molecular Weight	308.244
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC1=CC=C(Cl)C(OCC(O)CNC(C)(C)C)=C1

InChI

InChIKey=WJUUZHQWGKSLIJ-UHFFFAOYSA-N

InChI=1S/C14H22ClNO2.ClH/c1-10-5-6-12(15)13(7-10)18-9-11(17)8-16-14(2,3)4;/h5-7,11,16-17H,8-9H2,1-4H3;1H

HIDE SMILES / InChI

Description
Sources: http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?19/1/19484 | https://www.drugbank.ca/drugs/DB08808 | https://www.drugs.com/international/bupranolol.html | https://www.ncbi.nlm.nih.gov/pubmed/26456674

Bupranolol is a non-selective beta blocker without intrinsic sympathomimetic activity (ISA), but with strong membrane stabilizing activity. Bupranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension. Ophthalmic Bupranolol is used for the management of glaucoma and oral Bupranolol is used for the management of cardiovascular disorders. S-Bupranolol has also being shown to have superior preclinical safety profile and great antinociceptive efficacy and should be considered as a unique b-AR compound to advance future clinical pain studies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-2 adrenergic receptor 209 Target ID: CHEMBL210 Sources: https://www.drugbank.ca/drugs/DB08808 \| https://www.ncbi.nlm.nih.gov/pubmed/10079020 \| https://www.ncbi.nlm.nih.gov/pubmed/10411574	Antagonist 2849	5.2 nM [Ki]
Beta-1 adrenergic receptor 163 Target ID: CHEMBL213 Sources: https://www.drugbank.ca/drugs/DB08808 \| https://www.ncbi.nlm.nih.gov/pubmed/10079020 \| https://www.ncbi.nlm.nih.gov/pubmed/10411574	Antagonist 2849	50.0 nM [Ki]
Beta-3 adrenergic receptor 54 Target ID: CHEMBL246 Sources: https://www.drugbank.ca/drugs/DB08808 \| https://www.ncbi.nlm.nih.gov/pubmed/10411574 \| https://www.ncbi.nlm.nih.gov/pubmed/7903415	Antagonist 2849	170.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/381835 https://www.ncbi.nlm.nih.gov/pubmed/106216 https://www.ncbi.nlm.nih.gov/pubmed/2565296	Primary		Approved 8583	Betadrenol Approved Use Hypertension Launch Date 1968
Glaucoma 57 Sources: http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?19/1/19484 https://www.ncbi.nlm.nih.gov/pubmed/439706	Primary		Approved 8583	Ophtorenin Approved Use Glaucoma treatment

C_max

Value	Dose	Co-administered	Analyte	Population
2.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3028816/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BUPRANOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3028816/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BUPRANOLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3028816/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3028816/	Sources: https://pubmed.ncbi.nlm.nih.gov/3028816/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 65.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 66.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 59.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 59.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 3.0	yes [IC50 1.0964 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8820420/	yes [Km 0.27 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2475#section=BioAssay-Results Page: 6.0

PubMed

Title	Date	PubMed
Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor.	1993 Dec	7903415
Partial agonistic properties of (+/-)-pindolol at atypical beta-adrenoceptors in the guinea pig gastric fundus.	2001	11729357
Nebivolol induces calcium-independent signaling in endothelial cells by a possible beta-adrenergic pathway.	2001 Aug	11483868
Cardiovascular effects of beta 3-adrenoceptor stimulation in perinephritic hypertension.	2001 Aug	11473569
Functional properties of atypical beta-adrenoceptors on the guinea pig duodenum.	2001 Mar 23	11282125
Transdermal absorption of bupranolol in rabbit skin in vitro and in vivo.	2001 May	11379788
Upregulation of functional beta(3)-adrenergic receptor in the failing canine myocardium.	2001 Sep 28	11577025
beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current I(Ks) in guinea pig ventricular myocytes.	2002 Dec	12445880
The beta2- and beta3-adrenoceptor-mediated relaxation induced by fenoterol in guinea pig taenia caecum.	2002 Oct	12596892
Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion.	2003 Feb	12643612
Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta.	2003 Jan	12522078
[Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications].	2003 Oct-Dec	14971294
Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers.	2004 May	15060759
[Distribution and property of anti-beta3-adrenoceptor autoantibody in patients with heart failure].	2005 Dec	16563283
Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems.	2005 Jan 20	15620873
Adrenoceptor heterogeneity in the ruminal epithelium of sheep.	2005 May	15900505
Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin.	2005 May-Jun	16025846
Positive inotropic and lusitropic effects mediated via the low-affinity state of beta1-adrenoceptors in pithed rats.	2005 Nov	16151438
Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors.	2009 Mar	19439807

Patents

Sample Use Guides

In Vivo Use Guide

Bupranolol is usually given in doses of 100 mg twice daily in the treatment of hypertension

Route of Administration: Oral

In Vitro Use Guide

In the human detrusor bupranolol (a nonselective β-AR antagonist) at a low concentration (10(-8) M) did not inhibit isoproterenol-induced relaxation, but at higher concentrations (10(-7)-10(-5) M), the drug caused a rightward shift of the concentration-relaxation curve for isoproterenol in a dose-dependent manner

Name

Type

Language

BUPRANOLOL HYDROCHLORIDE

Common Name

English

BETADRAN

Preferred Name

English

Bupranolol hydrochloride [WHO-DD]

Common Name

English

1-(TERT-BUTYLAMINO)-3-((6-CHLORO-M-TOLYL)-OXY)-2-PROPANOL HYDROCHLORIDE

Systematic Name

English

LOOSER

Brand Name

English

PANIMIT

Brand Name

English

B 1312

Code

English

BETADRENOL

Brand Name

English

BUPRANOLOL HYDROCHLORIDE [MART.]

Common Name

English

KL-255

Code

English

KL-255 (AS HYDROCHLORIDE)

Code

English

BUPRANOLOL HYDROCHLORIDE [JAN]

Common Name

English

BUPRANOLOL HYDROCHLORIDE [MI]

Common Name

English

B-1312

Code

English

BUPRANOLOL HCL

Common Name

English

Code System Code Type Description

FDA UNII

DTC2G3GDPL