Identification

Name
Practolol
Accession Number
DB01297
Type
Small Molecule
Groups
Approved
Description

A beta-adrenergic antagonist that has been used in the emergency treatment of cardiac arrhythmias. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-Practolol
  • 1-(4-Acetamidophenoxy)-3-isopropylamino-2-propanol
  • 4'-(2-Hydroxy-3-(isopropylamino)propoxy)acetanilide
  • N-(4-(2-Hydroxy-3-((1-methylethyl)amino)propoxy)phenyl)acetamide
  • Practololum
  • Tocris-0831
Product Ingredients
IngredientUNIICASInChI Key
Practolol hydrochlorideAT88RXS5AE6996-43-6UEWORNJBQXFYSM-UHFFFAOYSA-N
Categories
UNII
SUG9176GRW
CAS number
6673-35-4
Weight
Average: 266.3361
Monoisotopic: 266.16304258
Chemical Formula
C14H22N2O3
InChI Key
DURULFYMVIFBIR-UHFFFAOYSA-N
InChI
InChI=1S/C14H22N2O3/c1-10(2)15-8-13(18)9-19-14-6-4-12(5-7-14)16-11(3)17/h4-7,10,13,15,18H,8-9H2,1-3H3,(H,16,17)
IUPAC Name
N-(4-{2-hydroxy-3-[(propan-2-yl)amino]propoxy}phenyl)acetamide
SMILES
CC(C)NCC(O)COC1=CC=C(NC(C)=O)C=C1

Pharmacology

Indication

Used in the emergency treatment of cardiac arrhythmias.

Pharmacodynamics

Practolol is a beta-adrenergic receptor antagonist that has been used in the emergency treatment of cardiac arrhythmias. Beta blockers inhibit normal epinephrine-mediated sympathetic actions, but have minimal effect on resting subjects. That is, they reduce the effect of excitement/physical exertion on heart rate and force of contraction and dilation of blood vessels.

Mechanism of action

Like other beta-adrenergic antagonists, practolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, practolol 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.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
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

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

Affected organisms
Not Available
Pathways
PathwayCategory
Practolol Action PathwayDrug action
Practolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may decrease the antihypertensive activities of Practolol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Practolol.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the atrioventricular blocking (AV block) activities of Practolol.
AcebutololAcebutolol may increase the hypotensive activities of Practolol.
AceclofenacAceclofenac may decrease the antihypertensive activities of Practolol.
AcemetacinAcemetacin may decrease the antihypertensive activities of Practolol.
AcepromazinePractolol may increase the orthostatic hypotensive activities of Acepromazine.
AceprometazineAceprometazine may increase the hypotensive activities of Practolol.
AcetohexamidePractolol may increase the hypoglycemic activities of Acetohexamide.
AcetylcholineThe risk or severity of adverse effects can be increased when Practolol is combined with Acetylcholine.
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015411
KEGG Drug
D05587
KEGG Compound
C11696
PubChem Compound
4883
PubChem Substance
46507496
ChemSpider
4715
BindingDB
25749
ChEBI
258351
ChEMBL
CHEMBL6995
Therapeutic Targets Database
DAP000940
PharmGKB
PA164752820
Wikipedia
Practolol
ATC Codes
C07AB01 — Practolol

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)134-136 °CPhysProp
logP0.79HANSCH,C ET AL. (1995)
Caco2 permeability-6.05ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.49 mg/mLALOGPS
logP0.53ALOGPS
logP0.83ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)14.03ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area70.59 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity75.24 m3·mol-1ChemAxon
Polarizability30.39 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9472
Blood Brain Barrier-0.8609
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.589
P-glycoprotein inhibitor INon-inhibitor0.8705
P-glycoprotein inhibitor IINon-inhibitor0.9147
Renal organic cation transporterNon-inhibitor0.9484
CYP450 2C9 substrateNon-substrate0.781
CYP450 2D6 substrateNon-substrate0.5082
CYP450 3A4 substrateNon-substrate0.6487
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.6103
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9289
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9268
Ames testNon AMES toxic0.9153
CarcinogenicityNon-carcinogens0.8402
BiodegradationNot ready biodegradable0.9564
Rat acute toxicity1.9187 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9917
hERG inhibition (predictor II)Non-inhibitor0.898
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/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dm-3900000000-6e93acc67e2905952d4e

Taxonomy

Description
This compound belongs to the class of organic compounds known as acetanilides. These are organic compounds containing an acetamide group conjugated to a phenyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Acetanilides
Alternative Parents
N-acetylarylamines / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Acetamides / Secondary carboxylic acid amides / Secondary alcohols / Amino acids and derivatives / 1,2-aminoalcohols / Dialkylamines
show 4 more
Substituents
Acetanilide / N-acetylarylamine / Phenoxy compound / N-arylamide / Phenol ether / Alkyl aryl ether / Acetamide / 1,2-aminoalcohol / Amino acid or derivatives / Carboxamide group
show 17 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
secondary alcohol, secondary amino compound, acetamides, ethanolamines, propanolamine (CHEBI:258351)

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. 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]
  2. Keyrilainen O, Uusitalo A: A comparative study of three beta 1-adrenoreceptor blocking drugs with different degree of intrinsic stimulating activity (metoprolol, practolol and H 87/07) in patients with angina pectoris. Ann Clin Res. 1978 Aug;10(4):185-90. [PubMed:30388]
  3. Saarnivaara L, Lindgren L, Hynynen M: Effects of practolol and metoprolol on QT interval, heart rate and arterial pressure during induction of anaesthesia. Acta Anaesthesiol Scand. 1984 Dec;28(6):644-8. [PubMed:6524278]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Buxton IL, Brunton LL: Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat. Circ Res. 1985 Jan;56(1):126-32. [PubMed:2857116]

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. 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 08:19 / Updated on August 02, 2018 04:34