Identification

Name
Bupranolol
Accession Number
DB08808
Type
Small Molecule
Groups
Experimental
Description

Bupranolol is a non-selective beta blocker without intrinsic sympathomimetic activity (ISA), but with strong membrane stabilizing activity. Its potency is similar to "propranolol":http://www.drugbank.ca/drugs/DB00571.

Structure
Thumb
Synonyms
  • Bupranol
Product Ingredients
IngredientUNIICASInChI Key
Bupranolol hydrochlorideDTC2G3GDPL15148-80-8WJUUZHQWGKSLIJ-UHFFFAOYSA-N
International/Other Brands
Betadrenol (Desma) / Ophtorenin (Winzer (Germany))
Categories
UNII
858YGI5PIT
CAS number
14556-46-8
Weight
Average: 271.783
Monoisotopic: 271.13390666
Chemical Formula
C14H22ClNO2
InChI Key
HQIRNZOQPUAHHV-UHFFFAOYSA-N
InChI
InChI=1S/C14H22ClNO2/c1-10-5-6-12(15)13(7-10)18-9-11(17)8-16-14(2,3)4/h5-7,11,16-17H,8-9H2,1-4H3
IUPAC Name
1-(tert-butylamino)-3-(2-chloro-5-methylphenoxy)propan-2-ol
SMILES
CC1=CC(OCC(O)CNC(C)(C)C)=C(Cl)C=C1

Pharmacology

Indication

Used to manage hypertension and tachycardia. Also used to treat glaucoma.

Pharmacodynamics

Bupranolol is a competitive, nonselective beta-blocker similar to propanolol without intrinsic sympathomimetic activity.

Mechanism of action

Bupranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.

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

Quickly and completely absorbed from the gut with less than 10% oral bioavailability.

Volume of distribution
Not Available
Protein binding

76%

Metabolism

Over 90% undergo first-pass metabolism. The main metabolite is carboxybupranolol, 4-chloro-3-[3-(1,1-dimethylethylamino)-2-hydroxy-propyloxy]benzoic acid, of which 88% are eliminated renally within 24 hours.

Route of elimination
Not Available
Half life

2-4 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include bradycardia, cardiac failure, hypotension, and brochospasm.

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

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may decrease the antihypertensive activities of Bupranolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Bupranolol.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the atrioventricular blocking (AV block) activities of Bupranolol.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Bupranolol.
AbediterolBupranolol may decrease the bronchodilatory activities of Abediterol.
AcebutololAcebutolol may increase the hypotensive activities of Bupranolol.
AceclofenacAceclofenac may decrease the antihypertensive activities of Bupranolol.
AcemetacinThe therapeutic efficacy of Bupranolol can be decreased when used in combination with Acemetacin.
AcepromazineBupranolol may increase the orthostatic hypotensive activities of Acepromazine.
AceprometazineAceprometazine may increase the hypotensive activities of Bupranolol.
Food Interactions
Not Available

References

Synthesis Reference

Kunz, W., Jacobi, H., Koch, C. and Geus, R.J.; U.S. Patent 3,309,406; March 14, 1967.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015697
KEGG Drug
D07590
PubChem Compound
2475
PubChem Substance
99445278
ChemSpider
2381
BindingDB
25765
ChEBI
135123
ChEMBL
CHEMBL305380
PharmGKB
PA165958426
IUPHAR
550
Guide to Pharmacology
GtP Drug Page
Wikipedia
Bupranolol
ATC Codes
C07AA19 — Bupranolol

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
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.143 mg/mLALOGPS
logP3.14ALOGPS
logP2.99ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area41.49 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity74.86 m3·mol-1ChemAxon
Polarizability30.35 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9784
Blood Brain Barrier-0.7572
Caco-2 permeable+0.5576
P-glycoprotein substrateSubstrate0.6384
P-glycoprotein inhibitor INon-inhibitor0.6857
P-glycoprotein inhibitor IINon-inhibitor0.8993
Renal organic cation transporterNon-inhibitor0.8713
CYP450 2C9 substrateNon-substrate0.8011
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.6373
CYP450 1A2 substrateInhibitor0.5416
CYP450 2C9 inhibitorNon-inhibitor0.8165
CYP450 2D6 inhibitorInhibitor0.6045
CYP450 2C19 inhibitorNon-inhibitor0.7218
CYP450 3A4 inhibitorNon-inhibitor0.8424
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5726
Ames testNon AMES toxic0.9025
CarcinogenicityNon-carcinogens0.8249
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4441 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9455
hERG inhibition (predictor II)Non-inhibitor0.6443
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 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 / Toluenes / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Toluene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / 1,2-aminoalcohol
show 15 more
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. Zelaszczyk D, Kozlowska H, Baranowska U, Baranowska M, Reutelsterz A, Kiec-Kononowicz K, Malinowska B, Schlicker E: Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors. J Physiol Pharmacol. 2009 Mar;60(1):51-60. [PubMed:19439807]
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. Lenard NR, Gettys TW, Dunn AJ: Activation of beta2- and beta3-adrenergic receptors increases brain tryptophan. J Pharmacol Exp Ther. 2003 May;305(2):653-9. Epub 2003 Jan 24. [PubMed:12606631]
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. 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. Lenard NR, Gettys TW, Dunn AJ: Activation of beta2- and beta3-adrenergic receptors increases brain tryptophan. J Pharmacol Exp Ther. 2003 May;305(2):653-9. Epub 2003 Jan 24. [PubMed:12606631]
  2. Matsushita M, Horinouchi T, Tanaka Y, Tsuru H, Koike K: Characterization of beta 3-adrenoceptor-mediated relaxation in rat abdominal aorta smooth muscle. Eur J Pharmacol. 2003 Dec 15;482(1-3):235-44. [PubMed:14660028]

Enzymes

Kind
Protein
Organism
Human
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. 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]
  2. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  3. 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]

Drug created on October 20, 2010 15:45 / Updated on October 01, 2018 16:30