Bevantolol

Targets (3)Enzymes (1)Biointeractions (4)

Identification

Name
Bevantolol
Accession Number
DB01295
Type
Small Molecule
Groups
Experimental
Description

Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension. Mechanism of Action Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors.

Structure
Thumb
3D
Similar Structures
Synonyms
  • (+-)-Bevantolol
  • 1-((2-(3,4-Dimethoxyphenyl)ethyl)amino)-3-(3-methylphenoxy)-2-propanol
  • 1-(3,4-Dimethoxyphenethylamino)-3-(m-tolyloxy)-2-propanol
  • 1-(3,4-Dimethoxyphenethylamino)-3-m-tolyloxy-propan-2-ol
  • 1-[2-(3,4-Dimethoxy-phenyl)-ethylamino]-3-m-tolyloxy-propan-2-ol
  • bevantolol
  • Bevantololum
Categories
UNII
34ZXW6ZV21
CAS number
59170-23-9
Weight
Average: 345.4327
Monoisotopic: 345.194008357
Chemical Formula
C20H27NO4
InChI Key
HXLAFSUPPDYFEO-UHFFFAOYSA-N
InChI
InChI=1S/C20H27NO4/c1-15-5-4-6-18(11-15)25-14-17(22)13-21-10-9-16-7-8-19(23-2)20(12-16)24-3/h4-8,11-12,17,21-22H,9-10,13-14H2,1-3H3
IUPAC Name
1-{[2-(3,4-dimethoxyphenyl)ethyl]amino}-3-(3-methylphenoxy)propan-2-ol
SMILES
COC1=C(OC)C=C(CCNCC(O)COC2=CC=CC(C)=C2)C=C1

Pharmacology

Indication

For the treatment of angina pectoris and hypertension.

Pharmacodynamics

Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension.

Mechanism of action

Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors. By binding and antagonizing beta-1 receptors Bevantolol inhibits the normal normal epinephrine-mediated sympathetic actions such as increased heart rate. This has the effect of decreasing preload and blood pressure.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Humans
UBeta-2 adrenergic receptor
antagonist
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Bevantolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidBevantolol may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Bevantolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Bevantolol.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Bevantolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Bevantolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Bevantolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe therapeutic efficacy of Bevantolol can be decreased when used in combination with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Bevantolol can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Bevantolol.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Bevantolol.
Food Interactions
Not Available

References

Synthesis Reference

Yutaka Nomura, "Process for preparation of bevantolol hydrochloride." U.S. Patent US5382689, issued December, 1974.

US5382689
General References
  1. Vaughan Williams EM: Bevantolol: a beta-1 adrenoceptor antagonist with unique additional actions. J Clin Pharmacol. 1987 Jul;27(7):450-60. [PubMed:2888789]
External Links
Human Metabolome Database
HMDB0015409
PubChem Compound
2372
PubChem Substance
46506014
ChemSpider
2282
ChEBI
238698
ChEMBL
CHEMBL314010
Therapeutic Targets Database
DAP000897
PharmGKB
PA164743236
Wikipedia
Bevantolol
ATC Codes
C07AB06 — BevantololC07BB06 — Bevantolol and thiazides

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)137-138 °CPhysProp
logP3.00HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0137 mg/mLALOGPS
logP2.83ALOGPS
logP3.03ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.31ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area59.95 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity98.54 m3·mol-1ChemAxon
Polarizability39.75 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8271
Blood Brain Barrier-0.9297
Caco-2 permeable-0.6012
P-glycoprotein substrateSubstrate0.8119
P-glycoprotein inhibitor IInhibitor0.625
P-glycoprotein inhibitor IIInhibitor0.8061
Renal organic cation transporterNon-inhibitor0.6935
CYP450 2C9 substrateNon-substrate0.7741
CYP450 2D6 substrateSubstrate0.5792
CYP450 3A4 substrateSubstrate0.5727
CYP450 1A2 substrateNon-inhibitor0.6261
CYP450 2C9 inhibitorNon-inhibitor0.9068
CYP450 2D6 inhibitorNon-inhibitor0.7311
CYP450 2C19 inhibitorNon-inhibitor0.9218
CYP450 3A4 inhibitorNon-inhibitor0.6133
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9339
Ames testNon AMES toxic0.9124
CarcinogenicityNon-carcinogens0.926
BiodegradationNot ready biodegradable0.8696
Rat acute toxicity2.0966 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6187
hERG inhibition (predictor II)Inhibitor0.8681
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as dimethoxybenzenes. These are organic aromatic compounds containing a monocyclic benzene moiety carrying exactly two methoxy groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Methoxybenzenes
Direct Parent
Dimethoxybenzenes
Alternative Parents
Phenethylamines / Phenoxy compounds / Anisoles / Toluenes / Aralkylamines / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds
show 1 more
Substituents
Dimethoxybenzene / O-dimethoxybenzene / Phenethylamine / Anisole / Phenol ether / Phenoxy compound / Alkyl aryl ether / Aralkylamine / Toluene / 1,2-aminoalcohol
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
propanolamine (CHEBI:238698)

Targets

Details1. Beta-1 adrenergic receptor
Kind
Protein
Organism
Humans
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. Hino T, Sakai K, Ichihara K, Abiko Y: Attenuation of ischaemia-induced regional myocardial acidosis by bevantolol, a beta 1-adrenoceptor antagonist, in dogs. Pharmacol Toxicol. 1989 Apr;64(4):324-8. [PubMed:2568629]
  2. Dukes ID, Vaughan Williams EM: Cardiovascular effects of bevantolol, a selective beta 1-adrenoceptor antagonist with a novel pharmacological profile. Br J Pharmacol. 1985 Feb;84(2):365-80. [PubMed:2858236]
  3. Lofdahl CG, Svedmyr K, Svedmyr N: Selectivity of bevantolol hydrochloride, a beta 1-adrenoceptor antagonist, in asthmatic patients. Pharmacotherapy. 1984 Jul-Aug;4(4):205-10. [PubMed:6148733]
  4. Vaughan Williams EM: Bevantolol: a beta-1 adrenoceptor antagonist with unique additional actions. J Clin Pharmacol. 1987 Jul;27(7):450-60. [PubMed:2888789]
  5. Horinouchi T, Morishima S, Tanaka T, Suzuki F, Tanaka Y, Koike K, Miwa S, Muramatsu I: Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol. Life Sci. 2007 Jul 12;81(5):399-404. Epub 2007 Jun 16. [PubMed:17628611]
Details2. Beta-2 adrenergic receptor
Kind
Protein
Organism
Humans
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. Horinouchi T, Morishima S, Tanaka T, Suzuki F, Tanaka Y, Koike K, Miwa S, Muramatsu I: Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol. Life Sci. 2007 Jul 12;81(5):399-404. Epub 2007 Jun 16. [PubMed:17628611]
Details3. Alpha-1A adrenergic receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Shiraishi K, Moriya M, Miyake N, Takayanagi I: Alpha 1-adrenoceptor blocking activities of bevantolol hydrochloride(NC-1400) and labetalol in rat isolated thoracic aorta--do they distinguish between subtypes? Gen Pharmacol. 1992 Sep;23(5):843-5. [PubMed:1358746]

Enzymes

Details1. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
No
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. 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]
  2. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  3. 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]

Drug created on June 30, 2007 08:18 / Updated on November 02, 2018 04:59