BUPRANOLOL

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H22ClNO2
Molecular Weight	271.783
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=HQIRNZOQPUAHHV-UHFFFAOYSA-N

InChI=1S/C14H22ClNO2/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

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
Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder.	2010-12	21221199
Pulsatile changes in free fatty acids augment hepatic glucose production and preserves peripheral glucose homeostasis.	2010-07	20424137
Comparison of the analysis of beta-blockers by different techniques.	2009-12-01	19879818
Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors.	2009-03	19439807
Amphiphilic poly{[alpha-maleic anhydride-omega-methoxy-poly(ethylene glycol)]-co-(ethyl cyanoacrylate)} graft copolymer nanoparticles as carriers for transdermal drug delivery.	2009	19918369
Influence of potent and selective beta-adrenoceptor agonist, CL 316243, on the contractile response of non-pregnant human myometrium.	2008-12	19261970
Impairment of NO-dependent relaxation in intralobar pulmonary arteries: comparison of urban particulate matter and manufactured nanoparticles.	2008-10	18941568
CGP12177-induced haemodynamic and vascular effects in normotensive and hypertensive rats.	2008-09-04	18601917
beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.	2008-09	18704193
Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion.	2008-07-09	18613981
Role of chemical structure in stereoselective recognition of beta-blockers by cyclodextrins in capillary zone electrophoresis.	2008-04-24	18022245
Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect of chemical penetration enhancers.	2008-01-30	18096189
Control of transdermal permeation of hydrocortisone acetate from hydrophilic and lipophilic formulations.	2008	18563577
The effects and selectivity of beta-adrenoceptor agonists in rat myometrium and urinary bladder.	2007-11-14	17632099
GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog.	2007-10	17626794
Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?	2007-06-01	17570158
Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells.	2007-04	17280840
Pharmacological characterization of the beta-adrenoceptor that mediates the relaxant response to noradrenaline in guinea-pig tracheal smooth muscle.	2007-03	17237919
Nebivolol in the treatment of chronic heart failure.	2007	18078016
Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor the vasodilator effect of cyanopindolol in the human pulmonary artery.	2006-09	17033087
Transdermal delivery of beta-blockers.	2006-05	16640500
[Distribution and property of anti-beta3-adrenoceptor autoantibody in patients with heart failure].	2005-12	16563283
Positive inotropic and lusitropic effects mediated via the low-affinity state of beta1-adrenoceptors in pithed rats.	2005-11	16151438
Functional coupling of beta3-adrenoceptors and large conductance calcium-activated potassium channels in human uterine myocytes.	2005-10	16014404
Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin.	2005-07-20	16025846
Comparison of the alpha-adrenoceptor-mediated effects of beta3-adrenoceptor ligands in rat pulmonary artery.	2005-06	16012871
Adrenaline produces the relaxation of guinea-pig airway smooth muscle primarily through the mediation of beta(2)-adrenoceptors.	2005-06	16006748
Adrenoceptor heterogeneity in the ruminal epithelium of sheep.	2005-05	15900505
Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems.	2005-01-20	15620873
Inconsistent role of nitric oxide on lipolysis in isolated rat adipocytes.	2005	15588153
Screening for library-assisted identification and fully validated quantification of 22 beta-blockers in blood plasma by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization.	2004-11-26	15595665
Aspartate138 is required for the high-affinity ligand binding site but not for the low-affinity binding site of the beta1-adrenoceptor.	2004-09	15322738
Endothelial beta3-adrenoceptors mediate vasorelaxation of human coronary microarteries through nitric oxide and endothelium-dependent hyperpolarization.	2004-08-24	15302798
ALpha1-adrenoceptor antagonist properties of CGP 12177A and other beta-adrenoceptor ligands: evidence against beta(3)- or atypical beta-adrenoceptors in rat aorta.	2004-06	15205310
Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers.	2004-05	15060759
Role of alpha-adrenergic receptors in the effect of the beta-adrenergic receptor ligands, CGP 12177, bupranolol, and SR 59230A, on the contraction of rat intrapulmonary artery.	2004-04	14718590
Effect of cyclodextrins on the complexation and transdermal delivery of bupranolol through rat skin.	2004-03-01	15129982
Overexpression of beta 1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for 'putative' beta 4-adrenoceptor pharmacology.	2004-03	14757703
[Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications].	2004-02-20	14971294
Atypical beta-adrenoceptors, different from beta 3-adrenoceptors and probably from the low-affinity state of beta 1-adrenoceptors, relax the rat isolated mesenteric artery.	2003-09	12967929
[Impairment of atypical beta-adrenergic-mediated relaxation in spontaneously hypertensive rats before and during the development of arterial hypertension].	2003-08-30	12945229
beta3-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human beta3-adrenergic receptor.	2003-08-01	12909312
Atypical cardiostimulant beta-adrenoceptor in the rat heart: stereoselective antagonism by bupranolol but lack of effect by some bupranolol analogues.	2003-08	12922943
Comparison between CL-316243- and CGP-12177A-induced relaxations in isolated canine ureter.	2003-07	12784085
The beta3-adrenoceptor-mediated relaxation induced by dopamine in guinea pig taenia caecum.	2003-06	14572171
Agonist actions of "beta-blockers" provide evidence for two agonist activation sites or conformations of the human beta1-adrenoceptor.	2003-06	12761341
Carazolol: a potent, selective beta 3-adrenoceptor agonist.	1995-11-30	8719421
Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor.	1993-12	7903415
Assessment of beta-blocking activity of low-dose bupranolol.	1989	2565296
[Betamed in the treatment of psychogenic disorders with a somatic component].	1983-09-30	6359726

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

Official Name

English

OPHTORENIN

Preferred Name

English

B-1312 FREE BASE

Code

English

KL-255 FREE BASE

Code

English

Bupranolol [WHO-DD]

Common Name

English

B 1312 FREE BASE

Code

English

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

Systematic Name

English

BUPRANOLOL [MI]

Common Name

English

bupranolol [INN]

Common Name

English

BUPRANOL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29576