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(OCC(O)CNC(C)C)C(=C1)C(C)=O
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 |
---|---|---|---|---|
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 |
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 |
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 |
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 |
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
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 |
|
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 |
|
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 |
|
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 |
|
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 |
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 |
|
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 |
|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
Acebutolol-induced ventricular tachycardia reversed with sodium bicarbonate. | 1999 |
|
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. | 2000 Apr |
|
Quantitative structure-retention and retention-activity relationships of beta-blocking agents by micellar liquid chromatography. | 2001 Apr 6 |
|
Evidence towards the role of arylamine N-acetyltransferase in Mycobacterium smegmatis and development of a specific antiserum against the homologous enzyme of Mycobacterium tuberculosis. | 2001 Dec |
|
First derivative spectrophotometric, TLC-densitometric, and HPLC determination of acebutolol HCL in presence of its acid-induced degradation product. | 2001 Feb |
|
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure. | 2001 Jun |
|
beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome. | 2001 Sep |
|
Isolation and properties of genetically defined strains of the methylotrophic yeast Hansenula polymorpha CBS4732. | 2002 Feb |
|
Mutations of muscle glycogen synthase that disable activation by glucose 6-phosphate. | 2002 Jan 15 |
|
Propranolol and metoprolol enhance the anticonvulsant action of valproate and diazepam against maximal electroshock. | 2002 Jan-Feb |
|
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 |
|
Changes in serum lipids and antioxidant status in west Algerian patients with essential hypertension treated with acebutolol compared to healthy subjects. | 2003 Aug |
|
Evaluation of teicoplanin chiral stationary phases of 3.5 and 5 microm inside diameter silica microparticles by polar-organic mode capillary electrochromatography. | 2003 Sep |
|
Spectrophotometric determination of some beta-blockers in dosage forms based on complex formation with Cu(II) and Co(II). | 2004 Jun |
|
[Cholinergic urticaria revealed by beta-blockers: case report and therapeutic management]. | 2005 Nov-Dec |
|
Transport of acebutolol through rabbit corneal epithelium. | 2006 Apr |
|
Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations. | 2006 Dec |
|
Transdermal delivery of beta-blockers. | 2006 May |
|
Stability of chosen beta-adrenolytic drugs of different polarity in basic environment. | 2008 Mar-Apr |
|
First record of Prorocentrum lima (Dinophyceae) inside harbor areas and along the Abruzzo region coast, W Adriatic. | 2009 Apr |
|
Application of ionic liquids in high performance reversed-phase chromatography. | 2009 Jun 4 |
|
Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
|
The role of transporters in the pharmacokinetics of orally administered drugs. | 2009 Sep |
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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NDF-RT |
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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m1290
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Acebutolol
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CHEMBL642
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40
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ACEBUTOLOL
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7107
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)