Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H28N2O4 |
Molecular Weight | 336.4259 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCC(=O)NC1=CC(C(C)=O)=C(OCC(O)CNC(C)C)C=C1
InChI
InChIKey=GOEMGAFJFRBGGG-UHFFFAOYSA-N
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)
Acebutolol is a cardioselective, beta-adrenoreceptor blocking agent, which possesses mild intrinsic sympathomimetic activity (ISA) in its therapeutically effective dose range. Acebutolol is marketed under the trade names Sectral, Prent. Acebutolol is indicated for the management of hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Acebutolol is also indicated in the management of ventricular premature beats; it reduces the total number of premature beats, as well as the number of paired and multiform ventricular ectopic beats, and R-on-T beats. 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.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2859774
Curator's Comment: Acebutolol is relatively hydrophilic and does not readily cross the blood-brain barrier, a fact that may be clinically significant in reducing the frequency and severity of central nervous system adverse effects.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
741.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | SECTRAL Approved UseINDICATIONS & USAGE HYPERTENSION: Acebutolol hydrochloride capsules are indicated for the management of hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. VENTRICULAR ARRHYTHMIAS: Acebutolol hydrochloride capsules are indicated in the management of ventricular premature beats; it reduces the total number of premature beats, as well as the number of paired and multiform ventricular ectopic beats, and R-on-T beats. Launch Date1984 |
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Primary | SECTRAL Approved UseINDICATIONS & USAGE HYPERTENSION: Acebutolol hydrochloride capsules are indicated for the management of hypertension in adults. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. VENTRICULAR ARRHYTHMIAS: Acebutolol hydrochloride capsules are indicated in the management of ventricular premature beats; it reduces the total number of premature beats, as well as the number of paired and multiform ventricular ectopic beats, and R-on-T beats. Launch Date1984 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
92 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6884417/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACEBUTOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4492 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6884417/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACEBUTOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4 h |
unknown, oral |
ACEBUTOLOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
74% |
unknown, oral |
ACEBUTOLOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
Other AEs: Breathing shallow, Nausea... Other AEs: Breathing shallow Sources: Nausea Pulse thready Tachycardia Bradycardia Asystole Death (grade 5) Blood pressure low |
9.2 g 1 times / day single, oral Overdose Dose: 9.2 g, 1 times / day Route: oral Route: single Dose: 9.2 g, 1 times / day Sources: |
healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: |
Other AEs: Blood pressure low, Heart rate low... Other AEs: Blood pressure low Sources: Heart rate low Necrosis bowel Muscle tone flaccid |
0.8 g 2 times / day multiple, oral Highest studied dose Dose: 0.8 g, 2 times / day Route: oral Route: multiple Dose: 0.8 g, 2 times / day Sources: |
unhealthy, 31-63 n = 11 Health Status: unhealthy Condition: hypertension Age Group: 31-63 Sex: M+F Population Size: 11 Sources: |
Disc. AE: Antinuclear antibody... AEs leading to discontinuation/dose reduction: Antinuclear antibody (3 patients) Sources: |
4 g 1 times / day single, oral Overdose Dose: 4 g, 1 times / day Route: oral Route: single Dose: 4 g, 1 times / day Sources: |
healthy, 43 n = 1 Health Status: healthy Age Group: 43 Sex: F Population Size: 1 Sources: |
Other AEs: Blood pressure low, Ventricular tachycardia... Other AEs: Blood pressure low Sources: Ventricular tachycardia Death (grade 5) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Asystole | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Blood pressure low | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Bradycardia | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Breathing shallow | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Nausea | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Pulse thready | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Tachycardia | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
|
Death | grade 5 | 6 g 1 times / day single, oral Overdose Dose: 6 g, 1 times / day Route: oral Route: single Dose: 6 g, 1 times / day Sources: |
healthy, 16 n = 1 Health Status: healthy Age Group: 16 Sex: F Population Size: 1 Sources: |
Blood pressure low | 9.2 g 1 times / day single, oral Overdose Dose: 9.2 g, 1 times / day Route: oral Route: single Dose: 9.2 g, 1 times / day Sources: |
healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: |
|
Heart rate low | 9.2 g 1 times / day single, oral Overdose Dose: 9.2 g, 1 times / day Route: oral Route: single Dose: 9.2 g, 1 times / day Sources: |
healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: |
|
Muscle tone flaccid | 9.2 g 1 times / day single, oral Overdose Dose: 9.2 g, 1 times / day Route: oral Route: single Dose: 9.2 g, 1 times / day Sources: |
healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: |
|
Necrosis bowel | 9.2 g 1 times / day single, oral Overdose Dose: 9.2 g, 1 times / day Route: oral Route: single Dose: 9.2 g, 1 times / day Sources: |
healthy, 24 n = 1 Health Status: healthy Age Group: 24 Sex: M Population Size: 1 Sources: |
|
Antinuclear antibody | 3 patients Disc. AE |
0.8 g 2 times / day multiple, oral Highest studied dose Dose: 0.8 g, 2 times / day Route: oral Route: multiple Dose: 0.8 g, 2 times / day Sources: |
unhealthy, 31-63 n = 11 Health Status: unhealthy Condition: hypertension Age Group: 31-63 Sex: M+F Population Size: 11 Sources: |
Blood pressure low | 4 g 1 times / day single, oral Overdose Dose: 4 g, 1 times / day Route: oral Route: single Dose: 4 g, 1 times / day Sources: |
healthy, 43 n = 1 Health Status: healthy Age Group: 43 Sex: F Population Size: 1 Sources: |
|
Ventricular tachycardia | 4 g 1 times / day single, oral Overdose Dose: 4 g, 1 times / day Route: oral Route: single Dose: 4 g, 1 times / day Sources: |
healthy, 43 n = 1 Health Status: healthy Age Group: 43 Sex: F Population Size: 1 Sources: |
|
Death | grade 5 | 4 g 1 times / day single, oral Overdose Dose: 4 g, 1 times / day Route: oral Route: single Dose: 4 g, 1 times / day Sources: |
healthy, 43 n = 1 Health Status: healthy Age Group: 43 Sex: F Population Size: 1 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
[Pharmacology of acebutolol in animals]. | 1975 Dec 31 |
|
[The comparison of clinical effectiveness of perindopril and acebutolol in the primary hypertension treatment]. | 2001 |
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Cardioselective beta-blocker use in patients with reversible airway disease. | 2001 |
|
Quantitative structure-retention and retention-activity relationships of beta-blocking agents by micellar liquid chromatography. | 2001 Apr 6 |
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First derivative spectrophotometric, TLC-densitometric, and HPLC determination of acebutolol HCL in presence of its acid-induced degradation product. | 2001 Feb |
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Effect of lipophilicity on in vivo iontophoretic delivery. II. Beta-blockers. | 2001 Jun |
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Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure. | 2001 Jun |
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[Interaction between melilot and acenocoumarol? (Melilotruscus aculeatus)]. | 2001 May-Jun |
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beta-Adrenoceptor blockade enhances the anticonvulsant effect of glutamate receptor antagonists against maximal electroshock. | 2001 Nov 16 |
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The effect of selective beta1-blockade on EMG signal characteristics during progressive endurance exercise. | 2002 Dec |
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Screening drugs for metabolic stability using pulsed ultrafiltration mass spectrometry. | 2002 Feb |
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Isolation and properties of genetically defined strains of the methylotrophic yeast Hansenula polymorpha CBS4732. | 2002 Feb |
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[Acebutolol in the treatment of arterial hypertension in pregnancy--comparison with commonly used hypertensive agents]. | 2002 Jan |
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[Acute poisoning with nifedipine and acebutol: two cases]. | 2003 |
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Influence of cimetidine co-administration on the pharmacokinetics of acebutolol enantiomers and its metabolite diacetolol in a rat model: the effect of gastric pH on double-peak phenomena. | 2003 Apr 14 |
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Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. | 2003 Aug |
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Changes in serum lipids and antioxidant status in west Algerian patients with essential hypertension treated with acebutolol compared to healthy subjects. | 2003 Aug |
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Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. | 2003 Aug |
|
Beta 1-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome. | 2003 Jan |
|
Atrial fibrillation in chronic dialysis patients in the United States: risk factors for hospitalization and mortality. | 2003 Jan 24 |
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Pharmacokinetic changes of acebutolol after oral administration in rabbits with diabetes mellitus induced by alloxan. | 2003 Jun |
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Agonist actions of "beta-blockers" provide evidence for two agonist activation sites or conformations of the human beta1-adrenoceptor. | 2003 Jun |
|
[Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications]. | 2003 Oct-Dec |
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Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier. | 2003 Sep |
|
Evaluation of teicoplanin chiral stationary phases of 3.5 and 5 microm inside diameter silica microparticles by polar-organic mode capillary electrochromatography. | 2003 Sep |
|
Determination of stability constants of the inclusion complexes of beta-blockers in heptakis (2,3-dimethyl-6-sulfato)-beta-cyclodextrin. | 2004 Dec |
|
Treatment of high blood pressure and gain in event-free life expectancy. | 2005 |
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Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations. | 2006 Dec |
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UPLC/MS for the identification of beta-blockers. | 2006 Feb 24 |
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Spectrofluorimetric determination of drugs containing active methylene group using N1-methyl nicotinamide chloride as a fluorigenic agent. | 2006 Jul |
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Transdermal delivery of beta-blockers. | 2006 May |
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Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride. | 2006 Nov |
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Arrhythmogenic right ventricular dysplasia in pregnancy: a case report. | 2006 Sep |
|
Smith-Magenis syndrome: a case report of improved sleep after treatment with beta1-adrenergic antagonists and melatonin. | 2006 Sep |
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Abstracts of papers presented at the 2007 pittsburgh conference. | 2007 |
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Cutaneous vasculitis induced by carvedilol. | 2007 Aug |
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A population-based analysis of the class effect of beta-blockers after myocardial infarction. | 2007 Feb |
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Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride. | 2007 Jan |
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Determination of beta-blockers and beta2-agonists in sewage by solid-phase extraction and liquid chromatography-tandem mass spectrometry. | 2007 May 4 |
|
Evaluation of the impact on entomocoenosis of active agents allowed in organic olive farming against Bactrocera oleae (Gmelin, 1790). | 2007 Sep-Oct |
|
Application of ionic liquids in high performance reversed-phase chromatography. | 2009 Jun 4 |
|
The role of transporters in the pharmacokinetics of orally administered drugs. | 2009 Sep |
|
Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis. | 2010 Feb 24 |
|
Principal component analysis of HPLC retention data and molecular modeling structural parameters of cardiovascular system drugs in view of their pharmacological activity. | 2010 Jul 9 |
|
Potential for biodegradation and sorption of acetaminophen, caffeine, propranolol and acebutolol in lab-scale aqueous environments. | 2010 Nov 15 |
|
Occurrence and removal of estrogens and beta blockers by various processes in wastewater treatment plants. | 2010 Sep 1 |
Sample Use Guides
Hypertension
The initial dosage of acebutolol in uncomplicated mild-to-moderate hypertension is 400 mg. This can be given as a single daily dose, but in occasional patients twice daily dosing may be required for adequate 24-hour blood-pressure control. An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day. Patients with more severe hypertension or who have demonstrated inadequate control may respond to a total of 1200 mg daily (administered b.i.d.), or to the addition of a second antihypertensive agent. Beta-1 selectivity diminishes as dosage is increased.
Ventricular Arrhythmia
The usual initial dose of acebutolol is 400 mg daily given as 200 mg b.i.d. Dosage should be increased gradually until an optimal clinical response is obtained, generally at 600 to 1200 mg per day. If treatment is to be discontinued, the dosage should be reduced gradually over a period of about two weeks.
Use in Older Patients
Older patients have an approximately 2-fold increase in bioavailability and may require lower maintenance doses. Doses above 800 mg/day should be avoided in the elderly.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6115715
Two adrenergic receptor antagonists, acebutolol and propranolol, were observed to depress rabbit heart contractile force and adrenaline-stimulated adenylate cyclase activity at 1 X 10-(5) to 1 X 10-(3) M and 1 X 10-(6) to 1 X 10-(3) M concentrations, respectively. Acebutolol depressed sarcoplasmic reticular and mitochondrial calcium uptake at 5 X 10-(3) to 10-(2) M concentrations.
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WHO-ATC |
C07AB04
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NDF-RT |
N0000175556
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N0000000161
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WHO-VATC |
QC07AB04
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LIVERTOX |
NBK548853
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WHO-ATC |
C07BB04
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NCI_THESAURUS |
C29576
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D000070
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C61525
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1978
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253-539-0
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DB01193
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SUB07371MIG
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m1290
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Acebutolol
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CHEMBL642
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ACEBUTOLOL
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7107
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)