Identification

Name
Betaxolol
Accession Number
DB00195  (APRD00245)
Type
Small Molecule
Groups
Approved, Investigational
Description

A cardioselective beta-1-adrenergic antagonist with no partial agonist activity.

Structure
Thumb
Synonyms
  • 1-(4-(2-(Cyclopropylmethoxy)ethyl)phenoxy)-3-((1-methylethyl)amino)-2-propanol
  • 1-(Isopropylamino)-3-[P-(cyclopropylmethoxyethyl)phenoxy]-2-propanol
  • betaxolol
  • Betaxololum
Product Ingredients
IngredientUNIICASInChI Key
Betaxolol Hydrochloride6X97D2XT0O63659-19-8CHDPSNLJFOQTRK-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Betoptic LiqLiquid0.5 %OphthalmicAlcon, Inc.1986-12-311997-07-31Canada
Betoptic SSuspension / drops2.8 mg/1mLOphthalmicALCON LABORATORIES, INC.1996-01-15Not applicableUs
Betoptic SSuspension0.25 %OphthalmicNovartis1994-12-31Not applicableCanada
KerloneTablet, film coated10 mg/1OralSanofi Aventis1989-10-272003-02-06Us
KerloneTablet, film coated20 mg/1OralSanofi Aventis1989-10-272003-02-06Us
Sandoz BetaxololSolution0.5 %OphthalmicSandoz Canada Incorporated1998-11-27Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BetaxololTablet, film coated10 mg/1OralMarlex Pharmaceuticals Inc2016-07-01Not applicableUs
BetaxololTablet, film coated20 mg/1OralGolden State Medical Supply2012-06-01Not applicableUs
BetaxololTablet, film coated20 mg/1OralPuraCap Laboratories LLC dba Blu Pharmaceuticals2016-08-22Not applicableUs
BetaxololTablet, film coated10 mg/1OralEpic Pharma, LLC2010-07-20Not applicableUs
BetaxololTablet, film coated10 mg/1OralPuraCap Laboratories LLC dba Blu Pharmaceuticals2016-08-22Not applicableUs
BetaxololTablet, film coated20 mg/1OralMarlex Pharmaceuticals Inc2016-07-01Not applicableUs
BetaxololTablet, film coated10 mg/1OralPhysicians Total Care, Inc.2003-10-07Not applicableUs
BetaxololTablet, film coated10 mg/1OralGolden State Medical Supply2012-06-01Not applicableUs
BetaxololSolution / drops5 mg/1mLOphthalmicAkorn2003-04-01Not applicableUs
BetaxololTablet, film coated20 mg/1OralEpic Pharma, LLC2010-07-20Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Betoptic/piloBetaxolol (0.25 %) + Pilocarpine hydrochloride (1.75 %)SuspensionOphthalmicAlcon, Inc.Not applicableNot applicableCanada
International/Other Brands
Betaxon / Betoptic / Kerlone
Categories
UNII
O0ZR1R6RZ2
CAS number
63659-18-7
Weight
Average: 307.4278
Monoisotopic: 307.214743799
Chemical Formula
C18H29NO3
InChI Key
NWIUTZDMDHAVTP-UHFFFAOYSA-N
InChI
InChI=1S/C18H29NO3/c1-14(2)19-11-17(20)13-22-18-7-5-15(6-8-18)9-10-21-12-16-3-4-16/h5-8,14,16-17,19-20H,3-4,9-13H2,1-2H3
IUPAC Name
1-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-3-[(propan-2-yl)amino]propan-2-ol
SMILES
CC(C)NCC(O)COC1=CC=C(CCOCC2CC2)C=C1

Pharmacology

Indication

For the management of hypertension.

Associated Conditions
Pharmacodynamics

Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.

Mechanism of action

Betaxolol selectively blocks catecholamine stimulation of beta(1)-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Betaxolol can also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles, causing bronchospasm.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
UBeta-2 adrenergic receptor
antagonist
Human
Absorption

Absorption of an oral dose is complete. There is a small and consistent first-pass effect resulting in an absolute bioavailability of 89% ± 5% that is unaffected by the concomitant ingestion of food or alcohol.

Volume of distribution
Not Available
Protein binding

50%

Metabolism

Primarily hepatic. Approximately 15% of the dose administered is excreted as unchanged drug, the remainder being metabolites whose contribution to the clinical effect is negligible.

Route of elimination
Not Available
Half life

14-22 hours

Clearance
Not Available
Toxicity

Oral LD50s are 350 to 400 mg betaxolol/kg in mice and 860 to 980 mg/kg in rats. Predicted symptoms of overdose include bradycardia, congestive heart failure, hypotension, bronchospasm, and hypoglycemia.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Betaxolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Betaxolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Betaxolol.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Betaxolol.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Betaxolol.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Betaxolol.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Betaxolol.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Betaxolol.
8-azaguanineThe serum concentration of 8-azaguanine can be increased when it is combined with Betaxolol.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be increased when it is combined with Betaxolol.
9-DeazaguanineThe serum concentration of 9-Deazaguanine can be increased when it is combined with Betaxolol.
Food Interactions
Not Available

References

Synthesis Reference

Ramesh Joshi, Muthukrishnan Murugan, Dinesh Garud, Sanjay Borikar, Mukund Gurjar, "PROCESS FOR PREPARATION OF S-(-)-BETAXOLOL AND SALTS THEREOF." U.S. Patent US20060004109, issued January 05, 2006.

US20060004109
General References
  1. Canotilho J, Castro RA: The structure of betaxolol studied by infrared spectroscopy and natural bond orbital theory. Spectrochim Acta A Mol Biomol Spectrosc. 2010 Aug;76(3-4):395-400. doi: 10.1016/j.saa.2010.03.038. Epub 2010 Apr 4. [PubMed:20418154]
External Links
Human Metabolome Database
HMDB0014341
KEGG Compound
C06849
PubChem Compound
2369
PubChem Substance
46506041
ChemSpider
2279
BindingDB
50405521
ChEBI
3082
ChEMBL
CHEMBL423
Therapeutic Targets Database
DAP000305
PharmGKB
PA448611
IUPHAR
549
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Betaxolol
ATC Codes
C07AB05 — BetaxololS01ED52 — Betaxolol, combinationsS01ED02 — Betaxolol
AHFS Codes
  • 52:40.08 — Beta-adrenergic Agents
FDA label
Download (111 KB)
MSDS
Download (38.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionDevelopment of Side Effects From Betaxolol1
3CompletedTreatmentGlaucoma / Ocular Hypertension2
3Unknown StatusTreatmentOpen-angle Glaucoma (OAG)1

Pharmacoeconomics

Manufacturers
  • Akorn inc
  • Bausch and lomb pharmaceuticals inc
  • Novex pharma
  • Wockhardt ltd
  • Alcon laboratories inc
  • Epic pharma llc
  • Kvk tech inc
  • Sanofi aventis us llc
  • Alcon inc
Packagers
  • Alcon Laboratories
  • Apotex Inc.
  • Dispensing Solutions
  • Falcon Pharmaceuticals Ltd.
  • GD Searle LLC
  • Golden State Medical Supply Inc.
  • Kaiser Foundation Hospital
  • KVK-Tech Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novex Pharma
  • Pharmedix
  • Physicians Total Care Inc.
  • Sanofi-Aventis Inc.
Dosage forms
FormRouteStrength
Solution / dropsOphthalmic5 mg/1mL
Tablet, film coatedOral10 mg/1
Solution / dropsOphthalmic5.6 mg/1mL
Tablet, coatedOral10 mg/1
Tablet, coatedOral20 mg/1
LiquidOphthalmic0.5 %
SuspensionOphthalmic0.25 %
Suspension / dropsOphthalmic2.8 mg/1mL
SuspensionOphthalmic
Tablet, film coatedOral20 mg/1
SolutionOphthalmic0.5 %
Prices
Unit descriptionCostUnit
Betoptic-S 0.25% Suspension 15ml Bottle195.44USD bottle
Betoptic-S 0.25% Suspension 10ml Bottle130.29USD bottle
Betaxolol HCl 0.5% Solution 15ml Bottle104.31USD bottle
Betoptic-S 0.25% Suspension 5ml Bottle51.99USD bottle
Betoptic s 0.25% eye drops9.79USD ml
Betaxolol hcl 0.5% eye drop6.82USD ml
Betoptic S 0.25 % Suspension2.54USD ml
Kerlone 20 mg tablet2.35USD tablet
Betaxolol 20 mg tablet1.86USD tablet
Kerlone 10 mg tablet1.63USD tablet
Betaxolol HCl 10 mg tablet1.29USD tablet
Betaxolol 10 mg tablet1.24USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5540918No1996-07-302014-01-30Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)70-72 °CPhysProp
water solubility451 mg/LNot Available
logP2.81RECANATINI,M (1992)
Caco2 permeability-4.81ADME Research, USCD
pKa9.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0298 mg/mLALOGPS
logP3ALOGPS
logP2.54ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area50.72 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity88.64 m3·mol-1ChemAxon
Polarizability37.05 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9903
Blood Brain Barrier-0.8906
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7683
P-glycoprotein inhibitor INon-inhibitor0.7967
P-glycoprotein inhibitor IINon-inhibitor0.8547
Renal organic cation transporterNon-inhibitor0.8206
CYP450 2C9 substrateNon-substrate0.8106
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.7221
CYP450 1A2 substrateInhibitor0.8972
CYP450 2C9 inhibitorInhibitor0.5241
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9249
CYP450 3A4 inhibitorNon-inhibitor0.9647
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9741
Ames testNon AMES toxic0.8765
CarcinogenicityNon-carcinogens0.9304
BiodegradationNot ready biodegradable0.9395
Rat acute toxicity2.1620 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7663
hERG inhibition (predictor II)Non-inhibitor0.7498
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0009000000-287e15a62fc0a0a17ccc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-1309000000-627420cbd67d8ac1e4ad
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fr-6900000000-e23f35ab4359c86dd966
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ab9-9800000000-0fec1fdb5cce29edc7de
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a6u-9600000000-35b64bf771f1c210f29d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0900-0619000000-76032f7e5f2fbe405815
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0209000000-891e6fe5f7380d1b7924

Taxonomy

Description
This compound belongs to the class of organic compounds known as tyrosols and derivatives. These are compounds containing a hydroxyethyl group attached to the C4 carbon of a phenol group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenols
Sub Class
Tyrosols and derivatives
Direct Parent
Tyrosols and derivatives
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Tyrosol derivative / Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / 1,2-aminoalcohol / Secondary alcohol / Dialkyl ether / Secondary amine / Secondary aliphatic amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
propanolamine (CHEBI:3082)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. McLean AJ, Zeng FY, Behan D, Chalmers D, Milligan G: Generation and analysis of constitutively active and physically destabilized mutants of the human beta(1)-adrenoceptor. Mol Pharmacol. 2002 Sep;62(3):747-55. [PubMed:12181453]
  2. Rudoy CA, Van Bockstaele EJ: Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1119-29. Epub 2007 Apr 19. [PubMed:17513029]
  3. Satoh N, Suzuki J, Bessho H, Kitada Y, Narimatsu A, Tobe A: Effects of betaxolol on cardiohemodynamics and coronary circulation in anesthetized dogs: comparison with atenolol and propranolol. Jpn J Pharmacol. 1990 Oct;54(2):113-9. [PubMed:2077180]
  4. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. [PubMed:2891463]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Rait JL: Systemic effects of topical ophthalmic beta-adrenoceptor antagonists. Aust N Z J Ophthalmol. 1999 Feb;27(1):57-64. [PubMed:10080340]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Betaxolol, Pediatric Care Solutions [Link]
  2. CYp1A3 CTEP document, cancer.gov [File]
  3. Companion Dx reference lab document: EXPANDED TEST OFFERING IN PHARMACOGENOMICS: CYP1A2 [File]
Details
2. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Zateyshchikov DA, Minushkina LO, Brovkin AN, Savel'eva EG, Zateyshchikova AA, Manchaeva BB, Nikitin AG, Sidorenko BA, Nosikov VV: Association of CYP2D6 and ADRB1 genes with hypotensive and antichronotropic action of betaxolol in patients with arterial hypertension. Fundam Clin Pharmacol. 2007 Aug;21(4):437-43. doi: 10.1111/j.1472-8206.2007.00518.x. [PubMed:17635183]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:39