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
[Betamed in the treatment of psychogenic disorders with a somatic component].	1983 Sep 30	6359726
Assessment of beta-blocking activity of low-dose bupranolol.	1989	2565296
Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor.	1993 Dec	7903415
Carazolol: a potent, selective beta 3-adrenoceptor agonist.	1995 Nov 30	8719421
Partial agonistic properties of (+/-)-pindolol at atypical beta-adrenoceptors in the guinea pig gastric fundus.	2001	11729357
Orthovanadate decreases leptin secretion from isolated mouse fat pads.	2001 Apr	11305589
Structure-activity relationship studies of (+/-)-terbutaline and (+/-)-fenoterol on beta3-adrenoceptors in the guinea pig gastric fundus.	2001 Aug	11885748
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
Beta(3)-adrenoceptors control Cl(-) conductance in rabbit nasal epithelium.	2001 Jun 22	11430932
Agonistic activity of SR59230A at atypical beta-adrenoceptors in guinea pig gastric fundus and duodenum.	2001 Mar 23	11282126
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
Synthesis and evaluation of radiolabeled antagonists for imaging of beta-adrenoceptors in the brain with PET.	2002 Feb	11738481
Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium.	2002 Jan	11815381
The beta2- and beta3-adrenoceptor-mediated relaxation induced by fenoterol in guinea pig taenia caecum.	2002 Oct	12596892
Orthovanadate decreases the leptin content in isolated mouse fat pads via proteasome activation.	2002 Oct 15	12361713
Beta2- and beta3-adrenoreceptor agonists: human myometrial selectivity and effects on umbilical artery tone.	2002 Sep	12237641
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.	2003 Apr	12658052
Atypical cardiostimulant beta-adrenoceptor in the rat heart: stereoselective antagonism by bupranolol but lack of effect by some bupranolol analogues.	2003 Aug	12922943
beta3-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human beta3-adrenergic receptor.	2003 Aug 1	12909312
Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion.	2003 Feb	12643612
Burst-like control of lipolysis by the sympathetic nervous system in vivo.	2003 Jan	12531882
Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta.	2003 Jan	12522078
Comparison between CL-316243- and CGP-12177A-induced relaxations in isolated canine ureter.	2003 Jul	12784085
[Impairment of atypical beta-adrenergic-mediated relaxation in spontaneously hypertensive rats before and during the development of arterial hypertension].	2003 Jul-Aug	12945229
Agonist actions of "beta-blockers" provide evidence for two agonist activation sites or conformations of the human beta1-adrenoceptor.	2003 Jun	12761341
Endothelial beta3-adrenoceptors mediate vasorelaxation of human coronary microarteries through nitric oxide and endothelium-dependent hyperpolarization.	2004 Aug 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 Jun	15205310
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 Nov 26	15595665
Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems.	2005 Jan 20	15620873
Functional coupling of beta3-adrenoceptors and large conductance calcium-activated potassium channels in human uterine myocytes.	2005 Oct	16014404
Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor the vasodilator effect of cyanopindolol in the human pulmonary artery.	2006 Sep	17033087
The effects and selectivity of beta-adrenoceptor agonists in rat myometrium and urinary bladder.	2007 Nov 14	17632099
Role of chemical structure in stereoselective recognition of beta-blockers by cyclodextrins in capillary zone electrophoresis.	2008 Apr 24	18022245
Influence of potent and selective beta-adrenoceptor agonist, CL 316243, on the contractile response of non-pregnant human myometrium.	2008 Dec	19261970
Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect of chemical penetration enhancers.	2008 Jan 30	18096189
Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion.	2008 Jul 9	18613981
Impairment of NO-dependent relaxation in intralobar pulmonary arteries: comparison of urban particulate matter and manufactured nanoparticles.	2008 Oct	18941568
beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.	2008 Sep	18704193
CGP12177-induced haemodynamic and vascular effects in normotensive and hypertensive rats.	2008 Sep 4	18601917
Amphiphilic poly{[alpha-maleic anhydride-omega-methoxy-poly(ethylene glycol)]-co-(ethyl cyanoacrylate)} graft copolymer nanoparticles as carriers for transdermal drug delivery.	2009	19918369
Comparison of the analysis of beta-blockers by different techniques.	2009 Dec 1	19879818
Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors.	2009 Mar	19439807
Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder.	2010 Dec	21221199
Pulsatile changes in free fatty acids augment hepatic glucose production and preserves peripheral glucose homeostasis.	2010 Jul	20424137

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