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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Acebutolol
- Accession Number
- DB01193 (APRD00772)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- 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.
- Structure
Structure for Acebutolol (DB01193)
- Synonyms
- (±)-acebutolol
- 3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide
- 5'-butyramido-2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenone
- Acebutolol
- Acebutololum
- Acetobutolol
- N-(3-acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl)butanamide
- N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide
- Product Ingredients
Ingredient UNII CAS InChI Key Acebutolol Hydrochloride B025Y34C54 34381-68-5 KTUFKADDDORSSI-UHFFFAOYSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Acebutolol Tablet 200 mg Oral Sanis Health Inc 2010-02-25 Not applicable Canada 
Acebutolol Tablet 100 mg Oral Sanis Health Inc 2010-02-25 Not applicable Canada Acebutolol Tablet 400 mg Oral Sanis Health Inc 2010-02-25 Not applicable Canada Acebutolol - 400 - Tab 400mg Tablet 400 mg Oral Pro Doc Limitee 1996-12-31 Not applicable Canada Acebutolol-100-tab 100mg Tablet 100 mg Oral Pro Doc Limitee 1996-12-31 Not applicable Canada Acebutolol-200 - Tab 200mg Tablet 200 mg Oral Pro Doc Limitee 1996-12-31 Not applicable Canada Monitan 100 Tablet 100 mg Oral Wyeth Ltd. 1995-12-31 2004-09-13 Canada Monitan 200 Tablet 200 mg Oral Wyeth Ltd. 1995-12-31 2007-01-22 Canada Monitan 400 Tablet 400 mg Oral Wyeth Ltd. 1994-12-31 2007-01-22 Canada Monitan Tab 200mg Tablet 200 mg Oral Wyeth Ltd. 1987-12-31 1996-09-10 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Acebutolol Hydrochloride Capsule 200 mg/1 Oral Major 2009-12-01 2018-09-13 US 
Acebutolol Hydrochloride Capsule 400 mg/1 Oral Amneal Pharmaceuticals of New York Llc 2009-12-01 Not applicable US Acebutolol Hydrochloride Capsule 200 mg/1 Oral AvKARE, Inc. 2009-12-14 Not applicable US Acebutolol Hydrochloride Capsule 400 mg/1 Oral Marlex Pharmaceuticals Inc 2017-10-20 Not applicable US Acebutolol Hydrochloride Capsule 200 mg/1 Oral Mylan Pharmaceuticals Inc. 1995-04-24 Not applicable US Acebutolol Hydrochloride Capsule 400 mg/1 Oral Physicians Total Care, Inc. 2005-04-22 Not applicable US Acebutolol Hydrochloride Capsule 200 mg/1 Oral Av Pak 2010-09-16 Not applicable US Acebutolol Hydrochloride Capsule 200 mg/1 Oral Amneal Pharmaceuticals LLC 2009-12-01 Not applicable US Acebutolol Hydrochloride Capsule 200 mg/1 Oral Marlex Pharmaceuticals Inc 2017-10-20 Not applicable US Acebutolol Hydrochloride Capsule 400 mg/1 Oral Av Pak 2010-09-16 2016-08-11 US - International/Other Brands
- Prent (Bayer)
- Categories
- Adrenergic Agents
- Adrenergic Antagonists
- Adrenergic beta-1 Receptor Antagonists
- Adrenergic beta-Antagonists
- Agents causing hyperkalemia
- Agents producing tachycardia
- Agents that produce hypertension
- Alcohols
- Amines
- Amino Alcohols
- Antiarrhythmic agents
- Antihypertensive Agents
- Autonomic Agents
- Beta Blocking Agents and Thiazides
- Beta Blocking Agents, Selective
- Beta Blocking Agents, Selective, and Thiazides
- Beta-Blockers (Beta1 Selective)
- Bradycardia-Causing Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Hypotensive Agents
- Moderate Risk QTc-Prolonging Agents
- Neurotransmitter Agents
- P-glycoprotein/ABCB1 Substrates
- Peripheral Nervous System Agents
- Phenoxypropanolamines
- Propanolamines
- Propanols
- QTc Prolonging Agents
- Sympathomimetics
- UNII
- 67P356D8GH
- CAS number
- 37517-30-9
- Weight
- Average: 336.4259
Monoisotopic: 336.204907394 - Chemical Formula
- C18H28N2O4
- InChI Key
- GOEMGAFJFRBGGG-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
Pharmacology
- Indication
For the management of hypertension and ventricular premature beats in adults.
- Associated Conditions
- Pharmacodynamics
Acebutolol 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 action
Acebutolol 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.
Target Actions Organism ABeta-1 adrenergic receptor partial agonistHumans UBeta-2 adrenergic receptor partial agonistHumans - Absorption
Well absorbed from the Gl tract with an absolute bioavailability of approximately 40% for the parent compound. In
- Volume of distribution
- Not Available
- Protein binding
26%
- Metabolism
Subject to extensive first-pass hepatic biotransformation (primarily to diacetolol).
- Route of elimination
Elimination 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 life
The plasma elimination half-life is approximately 3 to 4 hours. The half-life of its metabolite, diacetolol, is 8 to 13 hours.
- Clearance
- Not Available
- Toxicity
Symptoms 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
Pathway Category Acebutolol Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid Acebutolol may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 1-benzylimidazole The risk or severity of hypertension can be increased when Acebutolol is combined with 1-benzylimidazole. 1,10-Phenanthroline 1,10-Phenanthroline may increase the bradycardic activities of Acebutolol. 2,5-Dimethoxy-4-ethylamphetamine The therapeutic efficacy of Acebutolol can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine. 2,5-Dimethoxy-4-ethylthioamphetamine The therapeutic efficacy of Acebutolol 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 Acebutolol is combined with 3-isobutyl-1-methyl-7H-xanthine. 3,4-Methylenedioxyamphetamine The therapeutic efficacy of Acebutolol can be decreased when used in combination with 3,4-Methylenedioxyamphetamine. 4-Bromo-2,5-dimethoxyamphetamine The therapeutic efficacy of Acebutolol 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 Acebutolol. 5-methoxy-N,N-dimethyltryptamine The risk or severity of hypertension can be increased when Acebutolol is combined with 5-methoxy-N,N-dimethyltryptamine. - Food Interactions
- Take without regard to meals; absorption rate and maximal concentration are slightly reduced but the extent of absorption is not affected.
References
- Synthesis Reference
- US3857952
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015324
- KEGG Drug
- D02338
- KEGG Compound
- C06803
- PubChem Compound
- 1978
- PubChem Substance
- 46509113
- ChemSpider
- 1901
- BindingDB
- 25755
- ChEBI
- 2379
- ChEMBL
- CHEMBL642
- Therapeutic Targets Database
- DAP000484
- PharmGKB
- PA448011
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Acebutolol
- ATC Codes
- C07AB04 — Acebutolol
- C07AB — Beta blocking agents, selective
- C07A — BETA BLOCKING AGENTS
- C07 — BETA BLOCKING AGENTS
- C — CARDIOVASCULAR SYSTEM
- AHFS Codes
- 24:24.00 — Beta-adrenergic Blocking Agents
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Cardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases 1 3 Terminated Treatment Hemangiomas 1 4 Completed Treatment Healthy Volunteers 1 Not Available Completed Treatment Arrythmias / Nonvalvular Atrial Fibrillation 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Alphapharm Party Ltd.
- Amneal Pharmaceuticals
- Bryant Ranch Prepack
- Caremark LLC
- Kaiser Foundation Hospital
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Patheon Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Professional Co.
- Promius Pharma
- Dosage forms
Form Route Strength Capsule Oral 200 mg/1 Capsule Oral 400 mg/1 Tablet Oral 400 mg Tablet Oral 100 mg Tablet Oral 200 mg - Prices
Unit description Cost Unit Acebutolol hcl powder 7.08USD g Sectral 400 mg capsule 4.48USD capsule Sectral 200 mg capsule 3.37USD capsule Acebutolol HCl 400 mg capsule 1.39USD capsule Acebutolol 400 mg capsule 1.34USD capsule Sectral 400 mg Tablet 1.11USD tablet Acebutolol HCl 200 mg capsule 1.05USD capsule Acebutolol 200 mg capsule 1.01USD capsule Sectral 200 mg Tablet 0.56USD tablet Acebutolol 400 mg Tablet 0.51USD tablet Apo-Acebutolol 400 mg Tablet 0.51USD tablet Mylan-Acebutolol (Type S) 400 mg Tablet 0.51USD tablet Mylan-Acebutolol 400 mg Tablet 0.51USD tablet Novo-Acebutolol 400 mg Tablet 0.51USD tablet Nu-Acebutolol 400 mg Tablet 0.51USD tablet Rhotral 400 mg Tablet 0.51USD tablet Sectral 100 mg Tablet 0.37USD tablet Acebutolol 200 mg Tablet 0.26USD tablet Apo-Acebutolol 200 mg Tablet 0.26USD tablet Mylan-Acebutolol (Type S) 200 mg Tablet 0.26USD tablet Mylan-Acebutolol 200 mg Tablet 0.26USD tablet Novo-Acebutolol 200 mg Tablet 0.26USD tablet Nu-Acebutolol 200 mg Tablet 0.26USD tablet Rhotral 200 mg Tablet 0.26USD tablet Acebutolol 100 mg Tablet 0.17USD tablet Apo-Acebutolol 100 mg Tablet 0.17USD tablet Mylan-Acebutolol (Type S) 100 mg Tablet 0.17USD tablet Mylan-Acebutolol 100 mg Tablet 0.17USD tablet Novo-Acebutolol 100 mg Tablet 0.17USD tablet Nu-Acebutolol 100 mg Tablet 0.17USD tablet Rhotral 100 mg Tablet 0.17USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 136-138 Merck Index 13 water solubility 259 mg/L Not Available logP 1.71 HANSCH,C ET AL. (1995) Caco2 permeability -5.83 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.172 mg/mL ALOGPS logP 1.43 ALOGPS logP 1.53 ChemAxon logS -3.3 ALOGPS pKa (Strongest Acidic) 13.91 ChemAxon pKa (Strongest Basic) 9.57 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 87.66 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 94.87 m3·mol-1 ChemAxon Polarizability 38.51 Å3 ChemAxon Number of Rings 1 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 + 0.9156 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 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor 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
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 alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Alkyl-phenylketones
- Alternative Parents
- Acetophenones / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Aryl alkyl ketones / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Propargyl-type 1,3-dipolar organic compounds / Dialkylamines show 4 more
- Substituents
- Alkyl-phenylketone / Acetophenone / Benzoyl / Phenol ether / Aryl alkyl ketone / Phenoxy compound / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / 1,2-aminoalcohol show 16 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monocarboxylic acid amide, secondary amino compound, ether, aromatic amide, ethanolamines, propanolamine (CHEBI:2379)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- 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
- 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:2453744]
- 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:2568935]
- 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:16268148]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Partial agonist
- 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
- 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:16268148]
- 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:10433496]
- 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:8968966]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- 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]
- Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
- 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]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- 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:12948019]
- 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:8953513]
Drug created on June 13, 2005 07:24 / Updated on January 21, 2019 04:26