PENBUTOLOL

US Previously Marketed

First approved in 1987

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H29NO2
Molecular Weight	291.4284
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)NC[C@H](O)COC1=C(C=CC=C1)C2CCCC2

InChI

InChIKey=KQXKVJAGOJTNJS-HNNXBMFYSA-N

InChI=1S/C18H29NO2/c1-18(2,3)19-12-15(20)13-21-17-11-7-6-10-16(17)14-8-4-5-9-14/h6-7,10-11,14-15,19-20H,4-5,8-9,12-13H2,1-3H3/t15-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C18H29NO2
Molecular Weight	291.4284
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2183495 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf | https://www.drugbank.ca/drugs/DB01359

Penbutolol is a new beta-adrenergic blocking drug approved for the treatment of hypertension. It is a noncardioselective beta-blocker and has intrinsic sympathomimetic activity. Penbutolol is marketed under the trade names Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin. Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β1 adrenergic receptors and decreases heart rate, which lowers blood pressure. Levatol (Penbutolol) is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-1 adrenergic receptor 158 Target ID: CHEMBL213 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/2189902 \| https://www.ncbi.nlm.nih.gov/pubmed/11738481	Antagonist 2778
Beta-2 adrenergic receptor 203 Target ID: CHEMBL210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/2189902 \| https://www.ncbi.nlm.nih.gov/pubmed/11738481	Antagonist 2778
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL273 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568799	Antagonist 2778	2.4 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	Primary		Approved 8429	LEVATOL Approved Use Levatol® is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Launch Date 5.6782081E11

C_max

Value	Dose	Co-administered	Analyte	Population
285 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2906875	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		PENBUTOLOL blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2906875	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		PENBUTOLOL blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		PENBUTOLOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 mg 1 times / day single, intravenous Studied dose Dose: 4 mg, 1 times / day Route: intravenous Route: single Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6315039	unhealthy, 33- 62 years n = 10 Health Status: unhealthy Condition: ANGINA PECTORIS Age Group: 33- 62 years Sex: M Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6315039	Sources: https://pubmed.ncbi.nlm.nih.gov/6315039
120 mg 1 times / day steady, oral Studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6995132	unhealthy, 55.7 years (range: 43-64 years) n = 8 Health Status: unhealthy Age Group: 55.7 years (range: 43-64 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/6995132	Sources: https://pubmed.ncbi.nlm.nih.gov/6995132
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	Disc. AE: Asthenia, Nausea... AEs leading to discontinuation/dose reduction: Asthenia (0.6%) Nausea (0.8%) Depression (0.6%) Dizziness (0.6%) Headache (0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf

AEs

AE	Significance	Dose	Population
Asthenia	0.6% Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf
Depression	0.6% Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf
Dizziness	0.6% Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf
Headache	0.6% Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf
Nausea	0.8% Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf	unhealthy, adult n = 628 Health Status: unhealthy Age Group: adult Population Size: 628 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	UGT 192

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10048501/	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018976s012lbl.pdf#page=4 Page: 4.0	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00C706
ABI Chem	AC1L1XS5
ABI Chem	AC1Q59G2
AbovChem LLC	HY-B1154
Alfa Chemistry	AP38363325	https://reagents.alfa-chemistry.com/product/penbutolol-sulfate-cas-38363-32-5-10908.html
Angene	AGN-PC-0P32OW
BLD Pharm	BD146908
BOC Sciences	28163-36-2
BOC Sciences	36507-48-9
BOC Sciences	38363-32-5
BOC Sciences	38363-40-5
Chem Scene	CS-4758
Chemieliva Pharmaceutical Co., Ltd	PBCM1293955
Compound Cloud	37464
Compound Cloud	38010
Hangzhou Yuhao Chemical Technology	RT3441
Hangzhou Yuhao Chemical Technology	RT3469
Hangzhou Yuhao Chemical Technology	YH58368
HongKong Chemhere	SCD02081
LGC Standards	DRE-A15908910AL-100	https://www.lgcstandards.com/US/en/p/DRE-A15908910AL-100
LGC Standards	DRE-C15908910	https://www.lgcstandards.com/US/en/p/DRE-C15908910
Lab Network	LN01305404
Lab Network	LN01349069
MedChem Express	HY-B1154
MolPort	MolPort-046-418-593
MolPort	MolPort-046-589-958
MuseChem	I003413
MuseChem	M007889
MuseChem	R050593
MuseChem	R050597
NovoSeek	37464
Sigma Aldrich	32838
Sigma Aldrich	32838\|SIAL
Smolecule	S538944	http://www.smolecule.com/products/s538944
Synthonix	4233
THE BioTek	bt-278423	https://www.thebiotek.com/product/inhibitors/bt-278423
THE BioTek	bt-305398	https://www.thebiotek.com/product/others/bt-305398
Tetrahedron	TS35425
Toronto Research Chemicals	D453675
Toronto Research Chemicals	P220495
Toronto Research Chemicals	P220500
ZINC	ZINC000000001898	http://zinc15.docking.org/substances/ZINC000000001898
eMolecules	10681862
eMolecules	110068311
eMolecules	42854563
eMolecules	72973277
eMolecules	92272773
mcule	MCULE-1834926762
mcule	MCULE-3058866138
mcule	MCULE-5040019199
mcule	MCULE-7286074312

PubMed

Title	Date	PubMed
The effect of clonidine and penbutolol, respectively on catecholamines in blood and urine, plasma renin activity and urinary aldosterone in hypertensive patients.	1975 Feb	238481
Clinical electrophysiological properties of penbutolol: a non-selective beta-blocking agent.	1980	7439238
Single daily dose penbutolol in the treatment of hypertension: a double blind crossover comparison with propranolol.	1980 Jun	6995132
A comparative study of atenolol and penbutolol in hypertensive patients.	1983 Jul	6352272
[Validity of the use of penbutolol in essential arterial hypertension].	1990 Jun	2359502
Decrease in penbutolol central response as a cause of changes in its serum protein binding.	1990 Mar	1974610
Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism.	1990 May	2189902
(-)-Penbutolol as a blocker of central 5-HT1A receptor-mediated responses.	1992 Nov 3	1468487
Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents.	1994	8174208
High-performance liquid chromatography with chemiluminescence detection of penbutolol and its hydroxylated metabolite in rat plasma.	2001 Jun 15	11417867
5-HT receptor subtypes involved in the spinal antinociceptive effect of acetaminophen in rats.	2001 Nov 30	11734181
[Pharmacology of beta blockers and their significance for therapy of hypertension].	2002 Aug	12229254
Synthesis and evaluation of radiolabeled antagonists for imaging of beta-adrenoceptors in the brain with PET.	2002 Feb	11738481
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
Thermotropic liquid crystalline drugs.	2005 Jul	15969938
Clinical review: aggressive management and extracorporeal support for drug-induced cardiotoxicity.	2007	17367544
Stereospecific high-performance liquid chromatographic analysis of tramadol and its O-demethylated (M1) and N,O-demethylated (M5) metabolites in human plasma.	2007 Jun 1	17257910
Carvedilol in hypertension treatment.	2008	18629377
[Simultaneous determination of nine beta-agonist residues in animal derived foods by ultra performance liquid chromatography-tandem mass spectrometry].	2008 Nov	19253549
In vitro transdermal iontophoretic delivery of penbutolol sulfate.	2009 Jan	19555303
[Determination of fifteen beta-agonists in animal urine by high performance liquid chromatography-tandem mass spectrometry].	2010 Aug	21261043
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443

Patents

Sample Use Guides

In Vivo Use Guide

The usual starting and maintenance dose of Levatol (Penbutolol), used alone or in combination with other antihypertensive agents, such as thiazide-type diuretics, is 20 mg given once daily. Doses of 40 mg and 80 mg have been well-tolerated but have not been shown to give a greater antihypertensive effect. The full effect of a 20- or 40-mg dose is seen by the end of 2 weeks. A dose of 10 mg also lowers blood pressure, but the full effect is not seen for 4 to 6 weeks.

Route of Administration: Oral

In Vitro Use Guide

Penbutolol (20 uM) significantly inhibited both the increase in [Ca2+]i and the cell-shape change induced by 15 uM LPC in rat isolated cardiomyocytes..

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:52:16 UTC 2023` Edited by `admin` on `Sat Dec 16 16:52:16 UTC 2023`
Record UNII	78W62V43DY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PENBUTOLOL

Official Name

English

Penbutolol [WHO-DD]

Common Name

English

2-PROPANOL, 1-(2-CYCLOPENTYLPHENOXY)-3-((1,1-DIMETHYLETHYL)AMINO)-, (2S)-

Systematic Name

English

PENBUTOLOL [VANDF]

Common Name

English

PENBUTOLOL [MI]

Common Name

English

(-)-1-TERT-BUTYLAMINO-2-HYDROXY-3-(2'-CYCLOPENTYLPHENOXY)PROPANE

Common Name

English

penbutolol [INN]

Common Name

English

(2S)-1-(TERT-BUTYLAMINO)-3-(2-CYCLOPENTYLPHENOXY)PROPAN-2-OL

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

C07AA23