Identification

Name
Oxprenolol
Accession Number
DB01580
Type
Small Molecule
Groups
Approved
Description

A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.

Structure
Thumb
Synonyms
  • Oxprenololum
Product Ingredients
IngredientUNIICASInChI Key
Oxprenolol hydrochlorideF4XSI7SNIU6452-73-9COAJXCLTPGGDAJ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Slow Trasicor Tab 160mgTablet, extended release160 mgOralNovartis1981-12-312005-08-02Canada
Slow Trasicor Tab 80mgTablet, extended release80 mgOralNovartis1981-12-312005-08-02Canada
Trasicor Tab 20mgTablet20 mgOralNovartis1980-12-311999-08-04Canada
Trasicor Tab 40mgTablet40 mgOralNovartis1980-12-312008-01-22Canada
Trasicor Tab 80mgTablet80 mgOralNovartis1980-12-312009-02-25Canada
International/Other Brands
Trasacor / Trasicor
Categories
UNII
519MXN9YZR
CAS number
6452-71-7
Weight
Average: 265.348
Monoisotopic: 265.167793607
Chemical Formula
C15H23NO3
InChI Key
CEMAWMOMDPGJMB-UHFFFAOYSA-N
InChI
InChI=1S/C15H23NO3/c1-4-9-18-14-7-5-6-8-15(14)19-11-13(17)10-16-12(2)3/h4-8,12-13,16-17H,1,9-11H2,2-3H3
IUPAC Name
1-[2-(prop-2-en-1-yloxy)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol
SMILES
CC(C)NCC(O)COC1=CC=CC=C1OCC=C

Pharmacology

Indication

Used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.

Pharmacodynamics

Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity. Oxprenolol is a lipophilic beta blocker which passes the blood-brain barrier more easily than water soluble beta blockers. As such, it is associated with a higher incidence of CNS-related side effects than hydrophilic ligands such as atenolol, sotalol and nadolol. Oxprenolol is an potent beta-blocker and should not be administered to asthmatics because it can cause irreversible airway failure and inflammation.

Mechanism of action

Like other beta-adrenergic antagonists, oxprenolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, oxprenolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta-2 adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta-2 receptors in the juxtaglomerular apparatus, oxprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production. Oxprenolol therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
UBeta-2 adrenergic receptor
antagonist
Human
UBeta-3 adrenergic receptorNot AvailableHuman
Absorption

Oral bioavailability is 20-70%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life

1-2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include abdominal irritation, central nervous system depression, coma, extremely slow heartbeat, heart failure, lethargy, low blood pressure, and wheezing.

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

Interactions

Drug Interactions
DrugInteraction
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Oxprenolol.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Oxprenolol.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Oxprenolol.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Oxprenolol.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Oxprenolol is combined with 7-Nitroindazole.
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take without regard to meals.

References

General References
  1. McDevitt DG: Comparison of pharmacokinetic properties of beta-adrenoceptor blocking drugs. Eur Heart J. 1987 Dec;8 Suppl M:9-14. [PubMed:2897304]
External Links
Human Metabolome Database
HMDB0015520
PubChem Compound
4631
PubChem Substance
46508996
ChemSpider
4470
BindingDB
50240370
ChEBI
91704
ChEMBL
CHEMBL546
Therapeutic Targets Database
DAP000485
PharmGKB
PA10284
Wikipedia
Oxprenolol
ATC Codes
C07CA02 — Oxprenolol and other diureticsC07BA02 — Oxprenolol and thiazidesC07AA02 — Oxprenolol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, extended releaseOral160 mg
Tablet, extended releaseOral80 mg
TabletOral20 mg
TabletOral40 mg
TabletOral80 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.10HANSCH,C ET AL. (1995)
Caco2 permeability-4.68ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.68 mg/mLALOGPS
logP2.44ALOGPS
logP2.17ChemAxon
logS-2.6ALOGPS
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 Count9ChemAxon
Refractivity76 m3·mol-1ChemAxon
Polarizability30.31 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9817
Blood Brain Barrier-0.9759
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.6618
P-glycoprotein inhibitor INon-inhibitor0.5567
P-glycoprotein inhibitor IINon-inhibitor0.8945
Renal organic cation transporterNon-inhibitor0.8698
CYP450 2C9 substrateNon-substrate0.8122
CYP450 2D6 substrateNon-substrate0.5424
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9209
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8958
Ames testNon AMES toxic0.9367
CarcinogenicityNon-carcinogens0.9206
BiodegradationNot ready biodegradable0.9593
Rat acute toxicity2.5730 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9351
hERG inhibition (predictor II)Non-inhibitor0.7501
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/MSsplash10-006t-7920000000-1fed9f62e7ece1c8e951
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-3090000000-9ca7ccd0c0daba3c3040
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9110000000-b81a2c636a97b7a75df0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-9000000000-996746df1ffa4553b2db
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-9000000000-cc715f4401a8ea6f3c13
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-9000000000-7a6e78af4d59990c16da
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ab9-9000000000-986953ff107cdee4fc24

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Ether / Organic nitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Campbell CA, Parratt JR, Kane KA, Bullock G: Effects of prolonged administration of oxprenolol on severity of ischaemic arrhythmias, enzyme leakage, infarct size, and intracellular cardiac muscle action potentials. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):369-77. [PubMed:6202960]
  4. Lemmer B: [Pharmacological basis for the therapy of cardiovascular disease with beta-adrenoceptor blocking drugs (author's transl)]. Herz. 1982 Jun;7(3):168-78. [PubMed:6124492]
  5. Abrahamsson T: The beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat. Br J Pharmacol. 1986 Apr;87(4):657-64. [PubMed:2871880]
  6. 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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Sekut L, Champion BR, Page K, Menius JA Jr, Connolly KM: Anti-inflammatory activity of salmeterol: down-regulation of cytokine production. Clin Exp Immunol. 1995 Mar;99(3):461-6. [PubMed:7882570]
  4. Fujita H, Tanaka J, Maeda N, Sakanaka M: Adrenergic agonists suppress the proliferation of microglia through beta 2-adrenergic receptor. Neurosci Lett. 1998 Feb 6;242(1):37-40. [PubMed:9509999]
  5. Prinz M, Hausler KG, Kettenmann H, Hanisch U: beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in microglia. Brain Res. 2001 Apr 27;899(1-2):264-70. [PubMed:11311890]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name
ADRB3
Uniprot ID
P13945
Uniprot Name
Beta-3 adrenergic receptor
Molecular Weight
43518.615 Da
References
  1. Feve B, Emorine LJ, Lasnier F, Blin N, Baude B, Nahmias C, Strosberg AD, Pairault J: Atypical beta-adrenergic receptor in 3T3-F442A adipocytes. Pharmacological and molecular relationship with the human beta 3-adrenergic receptor. J Biol Chem. 1991 Oct 25;266(30):20329-36. [PubMed:1682311]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Sternieri E, Coccia CP, Pinetti D, Guerzoni S, Ferrari A: Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):981-1007. doi: 10.1517/17425255.2.6.981 . [PubMed:17125412]
  3. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  4. Iwaki M, Niwa T, Bandoh S, Itoh M, Hirose H, Kawase A, Komura H: Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432. doi: 10.1016/j.dmpk.2016.08.007. Epub 2016 Sep 2. [PubMed:27836712]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Dudley AJ, Bleasby K, Brown CD: The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK(1) cell monolayers. Br J Pharmacol. 2000 Sep;131(1):71-9. [PubMed:10960071]

Drug created on August 29, 2007 08:53 / Updated on November 02, 2018 08:46