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Identification
NameAcebutolol
Accession NumberDB01193  (APRD00772)
TypeSmall Molecule
GroupsApproved
Description

A cardioselective beta-adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm as well as weak inherent sympathomimetic action. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-AcebutololNot AvailableNot Available
(±)-acebutololNot AvailableNot Available
3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilideNot AvailableNot Available
5'-butyramido-2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenoneNot AvailableNot Available
AcebutololNot AvailableNot Available
AcebutololumNot AvailableNot Available
AcetobutololSpanishINN
N-(3-Acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl)butanamideNot AvailableNot Available
N-[3-Acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamideNot AvailableNot Available
Salts
Name/CAS Structure Properties
Acebutolol Hydrochloride
34381-68-5
Thumb
  • InChI Key:
  • Monoisotopic Mass:
  • Average Mass:
DBSALT000192
Brand names
NameCompany
PrentBayer
SectralWyeth
Brand mixturesNot Available
Categories
CAS number37517-30-9
WeightAverage: 336.4259
Monoisotopic: 336.204907394
Chemical FormulaC18H28N2O4
InChI KeyGOEMGAFJFRBGGG-UHFFFAOYSA-N
InChI
InChI=1S/C18H28N2O4/c1-5-6-18(23)20-14-7-8-17(16(9-14)13(4)21)24-11-15(22)10-19-12(2)3/h7-9,12,15,19,22H,5-6,10-11H2,1-4H3,(H,20,23)
IUPAC Name
N-(3-acetyl-4-{2-hydroxy-3-[(propan-2-yl)amino]propoxy}phenyl)butanamide
SMILES
CCCC(=O)NC1=CC(C(C)=O)=C(OCC(O)CNC(C)C)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilides
Direct parentAnilides
Alternative parentsAcetophenones; Benzoyl Derivatives; Phenol Ethers; Alkyl Aryl Ethers; Ketones; Secondary Alcohols; Secondary Carboxylic Acid Amides; 1,2-Aminoalcohols; Carboxylic Acids; Dialkylamines; Polyamines; Enolates
Substituentsphenol ether; benzoyl; alkyl aryl ether; ketone; carboxamide group; secondary carboxylic acid amide; 1,2-aminoalcohol; secondary alcohol; carboxylic acid; secondary amine; polyamine; secondary aliphatic amine; ether; enolate; carboxylic acid derivative; amine; carbonyl group; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Pharmacology
IndicationFor the management of hypertension and ventricular premature beats in adults.
PharmacodynamicsAcebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. In general, beta-blockers reduce the work the heart has to do and allow it to beat more regularly. Acebutolol has less antagonistic effects on peripheral vascular ß2-receptors at rest and after epinephrine stimulation than nonselective beta-antagonists. Low doses of acebutolol produce less evidence of bronchoconstriction than nonselective agents like propranolol but more than atenolol.
Mechanism of actionAcebutolol is a selective β1-receptor antagonist. Activation of β1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Acebutolol blocks these receptors, lowering the heart rate and blood pressure. This drug then has the reverse effect of epinephrine. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.
AbsorptionWell absorbed from the Gl tract with an absolute bioavailability of approximately 40% for the parent compound. In
Volume of distributionNot Available
Protein binding26%
Metabolism

Subject to extensive first-pass hepatic biotransformation (primarily to diacetolol).

Route of eliminationElimination via renal excretion is approximately 30% to 40% and by non-renal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall.
Half lifeThe plasma elimination half-life is approximately 3 to 4 hours. The half-life of its metabolite, diacetolol, is 8 to 13 hours.
ClearanceNot Available
ToxicitySymptoms of overdose include extreme bradycardia, advanced atrioventricular block, intraventricular conduction defects, hypotension, severe congestive heart failure, seizures, and in susceptible patients, bronchospasm, and hypoglycemia.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Acebutolol Action PathwayDrug actionSMP00296
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9156
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.8957
P-glycoprotein substrate Substrate 0.7378
P-glycoprotein inhibitor I Non-inhibitor 0.8557
P-glycoprotein inhibitor II Non-inhibitor 0.8664
Renal organic cation transporter Non-inhibitor 0.9466
CYP450 2C9 substrate Non-substrate 0.8102
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5752
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8721
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9639
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.849
Biodegradation Not ready biodegradable 0.8538
Rat acute toxicity 2.0487 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9821
hERG inhibition (predictor II) Non-inhibitor 0.8555
Pharmacoeconomics
Manufacturers
  • Amneal pharmaceutical
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
  • Promius pharma llc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Acebutolol hcl powder7.08USDg
Sectral 400 mg capsule4.48USDcapsule
Sectral 200 mg capsule3.37USDcapsule
Acebutolol HCl 400 mg capsule1.39USDcapsule
Acebutolol 400 mg capsule1.34USDcapsule
Sectral 400 mg Tablet1.11USDtablet
Acebutolol HCl 200 mg capsule1.05USDcapsule
Acebutolol 200 mg capsule1.01USDcapsule
Sectral 200 mg Tablet0.56USDtablet
Acebutolol 400 mg Tablet0.51USDtablet
Apo-Acebutolol 400 mg Tablet0.51USDtablet
Mylan-Acebutolol (Type S) 400 mg Tablet0.51USDtablet
Mylan-Acebutolol 400 mg Tablet0.51USDtablet
Novo-Acebutolol 400 mg Tablet0.51USDtablet
Nu-Acebutolol 400 mg Tablet0.51USDtablet
Rhotral 400 mg Tablet0.51USDtablet
Sectral 100 mg Tablet0.37USDtablet
Acebutolol 200 mg Tablet0.26USDtablet
Apo-Acebutolol 200 mg Tablet0.26USDtablet
Mylan-Acebutolol (Type S) 200 mg Tablet0.26USDtablet
Mylan-Acebutolol 200 mg Tablet0.26USDtablet
Novo-Acebutolol 200 mg Tablet0.26USDtablet
Nu-Acebutolol 200 mg Tablet0.26USDtablet
Rhotral 200 mg Tablet0.26USDtablet
Acebutolol 100 mg Tablet0.17USDtablet
Apo-Acebutolol 100 mg Tablet0.17USDtablet
Mylan-Acebutolol (Type S) 100 mg Tablet0.17USDtablet
Mylan-Acebutolol 100 mg Tablet0.17USDtablet
Novo-Acebutolol 100 mg Tablet0.17USDtablet
Nu-Acebutolol 100 mg Tablet0.17USDtablet
Rhotral 100 mg Tablet0.17USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point136-138Merck Index 13
water solubility259 mg/LNot Available
logP1.71HANSCH,C ET AL. (1995)
Caco2 permeability-5.83ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.172ALOGPS
logP1.43ALOGPS
logP1.53ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)13.91ChemAxon
pKa (Strongest Basic)9.57ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area87.66 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity94.87 m3·mol-1ChemAxon
Polarizability38.51 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3857952
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02338
KEGG CompoundC06803
PubChem Compound1978
PubChem Substance46509113
ChemSpider1901
BindingDB25755
ChEBI2379
ChEMBLCHEMBL642
Therapeutic Targets DatabaseDAP000484
PharmGKBPA448011
Drug Product Database2257599
RxListhttp://www.rxlist.com/cgi/generic2/ace.htm
Drugs.comhttp://www.drugs.com/cdi/acebutolol.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/sec1396.shtml
WikipediaAcebutolol
ATC CodesC07AB04
AHFS Codes
  • 24:24.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetohexamideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
ChlorpropamideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
ClonidineIncreased hypertension when clonidine stopped
DihydroergotamineIschemia with risk of gangrene
DisopyramideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
EpinephrineHypertension, then bradycardia
ErgonovineIschemia with risk of gangrene
ErgotamineIschemia with risk of gangrene
FenoterolAntagonism
FormoterolAntagonism
GliclazideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
GlipizideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
GlisoxepideThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
GlyburideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
IbuprofenRisk of inhibition of renal prostaglandins
IndacaterolBeta-adrenergic antagonists, especially those that are not cardioselective, may interfere with the effect of indacaterol when administered concurrently. Beta-blockers may exacerbate bronchospasms in patients with COPD.
IndomethacinRisk of inhibition of renal prostaglandins
Insulin AspartThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Insulin DetemirThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Insulin GlargineThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Insulin GlulisineThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Insulin LisproThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
IsoprenalineAntagonism
LidocaineThe beta-blocker, acebutolol, may increase the effect and toxicity of lidocaine.
MethysergideIschemia with risk of gangrene
OrciprenalineAntagonism
PipobromanAntagonism
PirbuterolAntagonism
PiroxicamRisk of inhibition of renal prostaglandins
PrazosinRisk of hypotension at the beginning of therapy
RepaglinideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
SalmeterolAntagonism
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TerbutalineAntagonism
TolazamideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
TolbutamideAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VerapamilIncreased effect of both drugs
Food Interactions
  • Take without regard to meals; absorption rate and maximal concentration are slightly reduced but the extent of absorption is not affected.

Targets

1. Beta-1 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: partial agonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

References:

  1. van den Meiracker AH, Man in ’t Veld AJ, Fischberg DJ, Molinoff PB, van Eck HJ, Boomsma F, Derkx FH, Schalekamp MA: Acute and long-term effects of acebutolol on systemic and renal hemodynamics, body fluid volumes, catecholamines, active renin, aldosterone, and lymphocyte beta-adrenoceptor density. J Cardiovasc Pharmacol. 1988 Apr;11(4):413-23. Pubmed
  2. Abrahamsson T: Characterization of the beta 1-adrenoceptor stimulatory effects of the partial beta 1-agonists acebutolol, xamoterol, H142/08 and H201/70. Eur J Pharmacol. 1989 May 2;164(1):121-8. Pubmed
  3. Fraysse B, Garric J: Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: partial agonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

References:

  1. Fraysse B, Garric J: Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6. Pubmed
  2. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. Pubmed
  3. Lima JJ: Relationship between beta adrenoceptor occupancy and receptor down-regulation induced by beta antagonists with intrinsic sympathomimetic activity. J Recept Signal Transduct Res. 1996 Sep-Nov;16(5-6):357-72. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  2. Terao T, Hisanaga E, Sai Y, Tamai I, Tsuji A: Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J Pharm Pharmacol. 1996 Oct;48(10):1083-9. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:21