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Acebutolol Hydrochloride
Also known as: 34381-68-5, Acebutolol hcl, Prent, Sectral, Neptal, Acebutolol (hydrochloride)
Molecular Formula
C18H29ClN2O4
Molecular Weight
372.9  g/mol
InChI Key
KTUFKADDDORSSI-UHFFFAOYSA-N
FDA UNII
B025Y34C54

A cardioselective beta-1 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.
1 2D Structure

Acebutolol Hydrochloride

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
N-[3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]butanamide;hydrochloride
2.1.2 InChI
InChI=1S/C18H28N2O4.ClH/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);1H
2.1.3 InChI Key
KTUFKADDDORSSI-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CCCC(=O)NC1=CC(=C(C=C1)OCC(CNC(C)C)O)C(=O)C.Cl
2.2 Other Identifiers
2.2.1 UNII
B025Y34C54
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Acebutolol

2. Acetobutolol

3. Apo Acebutolol

4. Apo-acebutolol

5. Apoacebutolol

6. M And B 17803 A

7. M And B 17803a

8. M And B-17803 A

9. M And B17803 A

10. Monitan

11. Neptal

12. Novo Acebutolol

13. Novo-acebutolol

14. Novoacebutolol

15. Prent

16. Rhotral

17. Sectral

2.3.2 Depositor-Supplied Synonyms

1. 34381-68-5

2. Acebutolol Hcl

3. Prent

4. Sectral

5. Neptal

6. Acebutolol (hydrochloride)

7. Acetanol

8. N-(3-acetyl-4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)butyramide Hydrochloride

9. Il-17803a

10. M&b 17803a

11. Nsc-757412

12. Mls000069553

13. N-[3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]butanamide;hydrochloride

14. Chebi:2380

15. 3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide Hydrochloride

16. Dl-1-(2-acetyl-4-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane Hydrochloride

17. B025y34c54

18. M&b-17803a

19. B 17803a

20. B-17803a

21. Smr000058800

22. (+-)-3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide Monohydrochloride

23. Dsstox_cid_25461

24. Dsstox_rid_80892

25. N-(3-acetyl-4-{2-hydroxy-3-[(propan-2-yl)amino]propoxy}phenyl)butanamide Hydrochloride

26. N-{3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}butanamide Hydrochloride

27. Dsstox_gsid_45461

28. Diasectral

29. Wesfalin

30. N-[3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]butanamide Hydrochloride

31. Acebutolol Hydrochloride [jan]

32. Ccris 1102

33. Sr-01000000133

34. Unii-b025y34c54

35. Hsdb 6524

36. Prestwick_512

37. Acebutolol Hydrochloride [usp:jan]

38. Einecs 251-980-3

39. Sectral (tn)

40. Il 17803a

41. M&b 17,803a

42. Opera_id_1259

43. Ncgc00016827-01

44. Cas-34381-68-5

45. Schembl41004

46. Mls001076107

47. Mls002222219

48. Mls002548874

49. Spectrum1500665

50. (+/-)-acebutolol Hydrochloride

51. Chembl1200813

52. Dtxsid5045461

53. Hms1568m19

54. Hms1921a06

55. Pharmakon1600-01500665

56. Bcp28416

57. Tox21_110633

58. Ac-002

59. Acebutolol Hydrochloride [mi]

60. Ccg-39278

61. Hy-17497a

62. Mfcd00078860

63. Nsc757412

64. S4010

65. Acebutolol Hydrochloride (jp17/usp)

66. Akos015895193

67. Tox21_110633_1

68. Ab03018

69. Acebutolol Hydrochloride [hsdb]

70. Ks-5245

71. Nc00669

72. Nsc 757412

73. Acebutolol Hydrochloride [mart.]

74. Acebutolol Hydrochloride [vandf]

75. S11992

76. Acebutolol Hydrochloride [usp-rs]

77. Acebutolol Hydrochloride [who-dd]

78. Ncgc00018215-06

79. Ncgc00094830-01

80. Ncgc00094830-02

81. Ncgc00094830-03

82. Ncgc00094830-04

83. Db-048610

84. Acebutolol Hydrochloride, Analytical Standard

85. Ft-0630582

86. Sw196705-3

87. Acebutolol Hydrochloride [ep Impurity]

88. Acebutolol Hydrochloride [orange Book]

89. Acebutolol Hydrochloride [ep Monograph]

90. Acebutolol Hydrochloride [usp Impurity]

91. Acebutolol Hydrochloride [usp Monograph]

92. C07677

93. D00597

94. 381a685

95. A822205

96. J-019577

97. Sr-01000000133-3

98. Q27105651

99. Acebutolol Hydrochloride 1.0 Mg/ml In Methanol (as Free Base)

100. Acebutolol Hydrochloride, European Pharmacopoeia (ep) Reference Standard

101. Acebutolol Hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material

102. Acebutolol Hydrochloride, United States Pharmacopeia (usp) Reference Standard

103. Dl-1-(2-acetyl-4-butyramido)-3-(isopropylamino)propan-2-ol Hydrochloride

104. (+/-)-3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)butyranilide Monohydrochloride

105. (1)-n-(3-acetyl-4-(2-hydroxy-3-((isopropyl)amino)propoxy)phenyl)butyramide Monohydrochloride

106. Butanamide, N-(3-acetyl-4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)phenyl)-, Monohydrochloride, (+-)-

107. Butanamide, N-(3-acetyl-4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)phenyl)-, Monohydrochloride, (+/-)-

108. Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]-, Hydrochloride (1:1)

109. Butyranilide, 3'-acetyl-4'-(2-hydroxy-3-(isopropylamino)propoxy)-, Monohydrochloride, (+-)-

110. N-(3-acetyl-4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)phenyl)-, Monohydrochloride, (+/-)-

111. N-[3-acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]butanamide Hydrochloride;acebutolol Hydrochloride

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 372.9 g/mol
Molecular Formula C18H29ClN2O4
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count5
Rotatable Bond Count10
Exact Mass372.1815851 g/mol
Monoisotopic Mass372.1815851 g/mol
Topological Polar Surface Area87.7 Ų
Heavy Atom Count25
Formal Charge0
Complexity401
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count2
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameAcebutolol hydrochloride
Drug LabelAcebutolol HCl is a selective, hydrophilic beta-adrenoreceptor blocking agent with mild intrinsic sympathomimetic activity for use in treating patients with hypertension and ventricular arrhythmias. It is marketed in capsule form for oral administrat...
Active IngredientAcebutolol hydrochloride
Dosage FormCapsule
RouteOral
Strengtheq 200mg base; eq 400mg base
Market StatusPrescription
CompanyAmneal Pharm; Mylan

2 of 2  
Drug NameAcebutolol hydrochloride
Drug LabelAcebutolol HCl is a selective, hydrophilic beta-adrenoreceptor blocking agent with mild intrinsic sympathomimetic activity for use in treating patients with hypertension and ventricular arrhythmias. It is marketed in capsule form for oral administrat...
Active IngredientAcebutolol hydrochloride
Dosage FormCapsule
RouteOral
Strengtheq 200mg base; eq 400mg base
Market StatusPrescription
CompanyAmneal Pharm; Mylan

4.2 Therapeutic Uses

Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


Acebutolol ... /is/ indicated in the treatment of classic angina pectoris, also referred to as "effort-associated angina". /NOT included in US product labeling/

MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 550


Acebutolol /is/ used in the treatment of mitral value prolapse syndrome. /NOT included in US product labeling/

MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 551


Acebutolol ... /is/ used for thyrotoxicosis. /NOT included in US product labeling/

MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 551


For more Therapeutic Uses (Complete) data for ACEBUTOLOL HYDROCHLORIDE (10 total), please visit the HSDB record page.


4.3 Drug Warning

Abrupt withdrawal of acebutolol may exacerbate angina symptoms or precipitate myocardial infarction in patients with corornary artery disease. Therefore, patients receiving acebutolol (especially those with ischemic heart disease) should be warned not to interrupt or discontinue therapy without consulting their physician. When acebutolol therapy is discontinued, patients should be monitored carefully and advised to temporarily limit their physical activity. If exacerbation of angina occurs after acebutolol therapy is interrupted, antianginal therapy should be reinstituted promptly, and appropriate measures for the management of unstable angina pectoris should be initiated. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue acebutolol therapy abruptly, even in patients receiving the drug for conditions other than angina.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1733


Since beta-adrenergic blocking agents may reduce cardiac output and precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease, acebutolol should be used with caution in these patients, and the patients should be observed for evidence of progression of arterial insufficiency.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1733


... It is recommended that acebutolol be used with caution in patients with diabetes mellitus (especially those with labile diabetes) since the drug also may mask signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, blood pressure changes, tremor, feelings of anxiety, but not sweating) and may potentiate insulin-induced hypoglycemia.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1734


Since beta-adrenergic blocking agents may inhibit bronchodilation produced by endogenous catecholamines, the drugs generally should not be used in patients with bronchospastic disease; however, because of its relative beta 1-selective adrenergic blocking activity, acebutolol may be used with caution in patients with bronchospastic disease who do not respond to or cannot tolerate other hypotensive agents.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1734


For more Drug Warnings (Complete) data for ACEBUTOLOL HYDROCHLORIDE (22 total), please visit the HSDB record page.


4.4 Minimum/Potential Fatal Human Dose

Death occurred after an 8.8 g overdose, whereas survival occurred with 7.6 and 9.6 g overdoses.

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 189


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Anti-Arrhythmia Agents

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)


Adrenergic beta-1 Receptor Antagonists

Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS. (See all compounds classified as Adrenergic beta-1 Receptor Antagonists.)


Antihypertensive Agents

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)


Sympathomimetics

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)


5.2 FDA Pharmacological Classification
5.2.1 Pharmacological Classes
beta-Adrenergic Blocker [EPC]; Adrenergic beta-Antagonists [MoA]
5.3 Absorption, Distribution and Excretion

Distribution of acebutolol hydrochloride into body tissue and fluids has not been fully characterized. Following IV administration in rats, acebutolol is distributed extensively into many tissues, including heart, liver, kidneys, lungs, intestines, stomach, and salivary glands, but only minimally into CSF or testes. Following oral administration of acebutolol hydrochloride in healthy individuals, acebutolol and, to a lesser extent, diacetolol, are distributed into saliva and minimally into CSF. Following oral administration of a single 300-mg dose of acebutolol hydrochloride, about 3-9% of the dose is distributed into bile within 24 hours, in approximately equivalent amounts as acebutolol and diacetolol. Peak biliary concentrations of acebutolol are approximately 60-100 times greater than peak plasma concentrations.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


Acebutolol and diacetolol readily cross the placenta and can accumulate in the fetus. In pregnant women receiving acebutolol, the mean acebutolol and diacetolol ratios of umbilical venous to maternal venous plasma concentrations were 0.8 (range: 0.5-1) and 0.6 (range: 0.3-0.8), respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


Following IV administration, acebutolol is rapidly and widely distributed into the extravascular space and the apparent volume of distribution of the drug in healthy adults is approximately 1.6-3 l/kg (range: 1-3.8 l/kg). In healthy individuals, the volume of distribution in the central compartment and at steady state averages 0.16-0.22 and approximately 1.2 l/kg, respectively, following IV administration. The apparent volume distribution may be decreased in geriatric patients.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


In vitro, acebutolol and diacetolol are approximately 11-35 and 6-9% bound, respectively, to plasma proteins at plasma acebutolol concentrations of 20-9,000 ng/ml. Acebutolol is approximately 50% bound to erythrocytes.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


For more Absorption, Distribution and Excretion (Complete) data for ACEBUTOLOL HYDROCHLORIDE (16 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

Acebutolol is rapidly and extensively metabolized in the liver. Acebutolol undergoes extensive hydrolysis of the butyramide group to form the desbutyl primary amine, acetolol, which is almost completely converted via N-acetylation to diacetolol. The extent of metabolism of acebutolol to diacetolol appears to be independent of the genetic acetylator phenotype of the patient. Diacetolol is equipotent to acebutolol and has a similar pharmacologic profile.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


5.5 Biological Half-Life

Following single or mutiple oral doses of acebutolol hydrochloride, the elimination half-life of diacetolol reportedly averages 21.5 hours (range: 11-49 hours) or 32 hours (range: 17-54 hours) in patients with creatinine clearances of 6-56 or less than 5 ml/minute, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


Following a single oral dose in healthy adults, the half-life of acebutolol in the initial distrubution phase (t1/2 alpha) is about 3 hours and the half-life in the terminal phase (t1/2 beta) has been reported to average 11 hours (range: 6-12 hours). The half-lives of the two identified metabolites, diacetolol and acetolol, average 7.5 (range: 7-11 hours) and 3 hours, respectively, following a single oral dose of the drug. The half-life of acebutolol tends to be slightly prolonged following multiple rather than single doses. Following multiple-dose oral administration of acebutolol hyrochloride in healthy individuals (400 mg twice daily for 56 days), the elimination half-life of acebutolol average 13 hours (range: 9-20 hours). The elimination half-lives of acebutolol and diacetolol may be slightly iincreased in geriatric patients.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


The plasma elimination half-lives of acebutolol and diacetolol in neonates born to women receiving the drug during pregnancy ranged from 6-14 and from 24-30 hours, respectively, in the first 24 hours after birth; the half-life of diacetolol decreased to 12-16 hours during the second day. Neonatal urinary excretion of the drug and diacetolol was maximal during the first 24 hours after birth.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1736


5.6 Mechanism of Action

Acebutolol is a beta-selective adrenergic blocking agent and has pharmacologic actions similar to those of other beta-adrenergic blocking agents. At low dosages, acebutolol selectively inhibits response to adrenergic stimuli by competively blocking cardiac beta1-adrenergic receptors, while having little effect on the beta2-adrenergic receptors of bronchial and vascular smooth muscle. At high dosages (eg, greater than 80 mg daily), the selectively of acebutolol for beta-1-adrenergic receptors usually diminishes, and the drug will competively inhibit beta-1- and beta-2-adrenergic receptors. The beta1-selective blocking activity of acebutolol appears to be more pronounced in animals than in humans. In vivo studies in animals and humans indicate that the relative beta-1-adrenergic blocking activity of acebutolol, on a weight basis, is approximately 10-30% that of propranolol, as determined by inhibition of reflex tachycardia in animals or inhibition of exercise or tilt-induced or reflex tachycardia in healthy individuals.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1735


In addition to inhibiting access of physiologic or synthetic catecholamines to beta-adrenergic receptors, acebutolol exhibits mild intrinsic sympathomimetic activity (partial beta-agonist activity). Acebutolol also has a membrane-stabilizing effect on the heart, which is similar to that of quinidine but occurs only at high plasma concentrations and usually is not apparent at dosages used clinically.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1735


The pharmacologic effects of acebutolol results from both the unchanged drug and its major metabolite, diacetolol. Diacetolol is equipotent to acebutolol and, in animals, has greater beta-selective adrenergic blocking activity than the parent drug. Diacetolol also has weak intrinsic sympathomimetic activity but does not have substantial membrane-stabilizing activity. Diacetolol may contribute substantially to the observed effects of acebutolol, since plasma concentrations of the metabolite are consistently higher than those of the parent during acebutolol therapy.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1735


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