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Identification
Name Betaxolol
Accession Number DB00195 (APRD00245)
Type small molecule
Groups approved
Description

A cardioselective beta-1-adrenergic antagonist with no partial agonist activity. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Betaxolol HCL
  • Betaxololum [INN-Latin]
  • Betazolol
Brand names
  • Betaxon
  • Betoptic
  • Betoptic S
  • Kerlone
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • EENT Drugs
CAS number 63659-18-7
Weight Average: 307.4278
Monoisotopic: 307.214743799
Chemical Formula C18H29NO3
InChI Key InChIKey=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
Plain Text
IUPAC Name
(3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-hydroxypropyl)(propan-2-yl)amine
SMILES
CC(C)NCC(O)COC1=CC=C(CCOCC2CC2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Phenyl Esters
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Cyclopropane and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For the management of hypertension.
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.
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
Pathway Name SMPDB ID
Smp00299 Betaxolol Pathway SMP00299
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
Dosage forms
Form Route Strength
Solution Ophthalmic
Suspension Ophthalmic
Prices
Unit description Cost Unit
Betoptic-S 0.25% Suspension 15ml Bottle 195.44 USD bottle
Betoptic-S 0.25% Suspension 10ml Bottle 130.29 USD bottle
Betaxolol HCl 0.5% Solution 15ml Bottle 104.31 USD bottle
Betoptic-S 0.25% Suspension 5ml Bottle 51.99 USD bottle
Betoptic s 0.25% eye drops 9.79 USD ml
Betaxolol hcl 0.5% eye drop 6.82 USD ml
Betoptic S 0.25 % Suspension 2.54 USD ml
Kerlone 20 mg tablet 2.35 USD tablet
Betaxolol 20 mg tablet 1.86 USD tablet
Kerlone 10 mg tablet 1.63 USD tablet
Betaxolol HCl 10 mg tablet 1.29 USD tablet
Betaxolol 10 mg tablet 1.24 USD tablet
Patents
Country Patent Number Approved Expires
United States 5540918 1994-01-30 2014-01-30
Properties
State solid
Melting point 70-72 oC
Experimental Properties
Property Value Source
water solubility 451 mg/L PhysProp
logP 2.4 PhysProp
Caco2 permeability -4.81 [ADME Research, USCD] BiGG
pKa 9.4 Various sources
Predicted Properties
Property Value Source
water solubility 2.98e-02 g/l ALOGPS
logP 3.00 ALOGPS
logP 2.54 ChemAxon Molconvert
logS -4.01 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 50.72 ChemAxon Molconvert
rotatable bond count 11 ChemAxon Molconvert
refractivity 88.64 ChemAxon Molconvert
polarizability 37.05 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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. Epub 2010 Apr 4. Pubmed
External Links
Resource Link
KEGG Compound C06849 Link_out
PubChem Compound 2369 Link_out
PubChem Substance 46506041 Link_out
ChemSpider 2279 Link_out
BindingDB 50026854 Link_out
ChEBI 3082 Link_out
ChEMBL 3082 Link_out
Therapeutic Targets Database DAP000305 Link_out
PharmGKB PA448611 Link_out
Drug Product Database 2235971 Link_out
RxList http://www.rxlist.com/cgi/generic3/betaxolol.htm Link_out
Drugs.com http://www.drugs.com/cdi/betaxolol-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Betaxolol Link_out
ATC Codes
  • C07AB05
  • S01ED02
AHFS Codes
  • 52:92.00
PDB Entries Not Available
FDA label show (111.2 KB)
MSDS show (38.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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 equal affinity

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  4. Lesar TS: Comparison of ophthalmic beta-blocking agents. Clin Pharm. 1987 Jun;6(6):451-63. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Beta-2 adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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 30-fold greater affinity than it does norepinephrine

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rait JL: Systemic effects of topical ophthalmic beta-adrenoceptor antagonists. Aust N Z J Ophthalmol. 1999 Feb;27(1):57-64. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Actions: substrate, inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:01

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.