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

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
Bévantolol
Bevantololum

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Bevantolol hydrochloride	4VB9HU07BC	42864-78-8	FJTKCFSPYUMXJB-UHFFFAOYSA-N

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.

Target	Actions	Organism
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

Pathway	Category
Bevantolol Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid	Bevantolol may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazole	1-benzylimidazole may decrease the antihypertensive activities of Bevantolol.
2,5-Dimethoxy-4-ethylamphetamine	The therapeutic efficacy of Bevantolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The therapeutic efficacy of Bevantolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine	The risk or severity of adverse effects can be increased when Bevantolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,5-diiodothyropropionic acid	The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Bevantolol.
4-Bromo-2,5-dimethoxyamphetamine	The therapeutic efficacy of Bevantolol can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine	The therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Bevantolol.
5-methoxy-N,N-dimethyltryptamine	5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Bevantolol.
6-O-benzylguanine	The risk or severity of adverse effects can be increased when Bevantolol is combined with 6-O-benzylguanine.

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

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 — Bevantolol

C07BB06 — 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

Property	Value	Source
melting point (°C)	137-138 °C	PhysProp
logP	3.00	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	0.0137 mg/mL	ALOGPS
logP	2.83	ALOGPS
logP	3.03	ChemAxon
logS	-4.4	ALOGPS
pKa (Strongest Acidic)	14.09	ChemAxon
pKa (Strongest Basic)	9.31	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	59.95 Å²	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	98.54 m³·mol^-1	ChemAxon
Polarizability	39.75 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.8271
Blood Brain Barrier	-	0.9297
Caco-2 permeable	-	0.6012
P-glycoprotein substrate	Substrate	0.8119
P-glycoprotein inhibitor I	Inhibitor	0.625
P-glycoprotein inhibitor II	Inhibitor	0.8061
Renal organic cation transporter	Non-inhibitor	0.6935
CYP450 2C9 substrate	Non-substrate	0.7741
CYP450 2D6 substrate	Substrate	0.5792
CYP450 3A4 substrate	Substrate	0.5727
CYP450 1A2 substrate	Non-inhibitor	0.6261
CYP450 2C9 inhibitor	Non-inhibitor	0.9068
CYP450 2D6 inhibitor	Non-inhibitor	0.7311
CYP450 2C19 inhibitor	Non-inhibitor	0.9218
CYP450 3A4 inhibitor	Non-inhibitor	0.6133
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9339
Ames test	Non AMES toxic	0.9124
Carcinogenicity	Non-carcinogens	0.926
Biodegradation	Not ready biodegradable	0.8696
Rat acute toxicity	2.0966 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Strong inhibitor	0.6187
hERG inhibition (predictor II)	Inhibitor	0.8681

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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 compoundsHydrocarbon derivatives
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

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]
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]
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]
Vaughan Williams EM: Bevantolol: a beta-1 adrenoceptor antagonist with unique additional actions. J Clin Pharmacol. 1987 Jul;27(7):450-60. [PubMed:2888789]
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

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

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

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]
Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
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 April 03, 2019 12:59

Bevantolol

Identification

Structure for Bevantolol (DB01295)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

Enzymes

References