Acebutolol is a beta-blocker that is used to treat cardiac arrhythmias and high blood pressure. In rats, acebutolol (10 mg/kg) had a plasma clearance rate of 61.9 mL/min/kg, a volume of distribution of 9.6 L/kg, and an elimination half-life of 1.8 hours. In rats, acebutolol (50 mg/kg) had a plasma clearance rate of 46.5 mL/min/kg, a volume of distribution of 9.5 L/kg, and an elimination half-life of 2.3 hours [1]. In Sprague-Dawley rats, acebutolol (30 mg/kg) reduced cardiac output by 65% and 31% after measurements at 1 and 10 minutes, respectively. Acebutolol (30 mg/kg) significantly reduced regional blood flow (RBF) in most organs measured at 1 or 10 minutes compared with baseline values in Sprague-Dawley rats.

Absorption, Distribution and Excretion
This product is well absorbed from the gastrointestinal tract, with an absolute bioavailability of approximately 40% for the parent compound. Renal excretion accounts for approximately 30% to 40%, while non-renal excretion mechanisms account for 50% to 60%, including bile excretion and direct cross-section of the intestinal wall. Metabolism/Metabolites Primarily metabolized via first-pass metabolism in the liver (mainly converted to diacetylvolol). Biological Half-Life The plasma elimination half-life is approximately 3 to 4 hours. The half-life of its metabolite, diacetylvolol, is 8 to 13 hours.

Hepatotoxicity
Mild to moderate elevations in serum transaminase levels are rare during acebutolol treatment. These elevations are usually asymptomatic and transient, returning to normal with continued treatment. Clinically significant cases of acute liver injury caused by acebutolol are rarely documented. Liver injury typically appears within 1 to 6 weeks of starting treatment. The pattern of liver enzyme elevation is usually hepatocellular, presenting with symptoms similar to acute hepatitis, although some cases present with mixed enzyme elevations. Fever is usually associated with liver injury but is generally not accompanied by rash or eosinophilia. Acebutolol is known to induce autoantibodies, such as antinuclear antibodies, in 10% to 30% of patients, some of whom develop lupus-like syndromes presenting with fatigue, rash, and arthralgia. Serum enzyme elevations may accompany this syndrome, but jaundice and symptoms of liver injury are uncommon. Published cases of acebutolol-induced hepatotoxicity are relatively mild, self-limiting, and recover rapidly after discontinuation of the drug. Re-administration of the drug leads to rapid recurrence of liver injury.
Probability Score: C (Possibly due to clinically significant liver damage).

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Effects during Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Because acebutolol and its active metabolite diacetylolol are excreted in large quantities into breast milk, and there are reports of adverse reactions in breastfed infants, alternative medications are recommended, especially when breastfeeding newborns or premature infants.
◉ Effects on Breastfed Infants
A study of mothers taking beta-blockers while breastfeeding found a numerically increased number of adverse reactions in mothers taking any beta-blocker, but this was not statistically significant. Although the ages of affected infants were matched with those in the control group, the ages of the affected infants were not specified. One mother reported that her breastfed infant (age not specified) did not experience adverse reactions during acebutolol use.
One newborn experienced hypotension, bradycardia, and transient tachypnea, possibly due to the presence of acebutolol and diacetylolol in breast milk. The mother was taking 400 mg of acebutolol daily and had renal impairment. No adverse reactions were observed in two other breastfed newborns reported in this report. One mother with essential hypertension had been taking acebutolol for several years. She continued taking the medication during her first pregnancy and while breastfeeding. Her infant was generally healthy but appeared to have decreased muscle tone. After she stopped taking the medication, the infant still experienced wheezing and possible sleep apnea. She also took acebutolol during her second pregnancy, but her blood pressure was poorly controlled, ultimately resulting in a cesarean section. Aside from decreased muscle tone (including limb extension), incomplete Moro reflex, and significant head tilting, the infant was in good condition in the neonatal intensive care unit (NICU). The infant was not breastfed. The late postpartum adverse reaction in the first infant was likely caused by acebutol and diacetylolol in breast milk, but plasma drug concentrations in the infant were not detected. ◉ Effects on lactation and breast milk
As of the revision date, no published information was found regarding the effects of beta-blockers or acebutolol during normal breastfeeding. A study of six patients with hyperprolactinemia and galactorrhea found that serum prolactin levels did not change after β-adrenergic blockade with propranolol.

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Protein binding rate
26%

[1]. Piquette-Miller, M. and F. Jamali, Pharmacokinetics and multiple peaking of acebutolol enantiomers in rats. Biopharm Drug Dispos, 1997. 18(6): p. 543-56.
[2]. Bristow MR, et al. Treatment of chronic heart failure with β-adrenergic receptor antagonists: a convergence of receptor pharmacology and clinical cardiology. Circ Res. 2011 Oct 28;109(10):1176-94.
[3]. Mostafavi, S., R. Lewanczuk, and R. Foster, Influence of acebutolol and metoprolol on cardiac output and regional blood flow in rats. Biopharm Drug Dispos, 2000. 21(4): p. 121-8.

Acebutolol is an ether compound, specifically the 2-acetyl-4-(butyrylamino)phenyl ether of the primary hydroxyl group of 3-(propyl-2-ylamino)propane-1,2-diol. It acts as a β-adrenergic antagonist, antiarrhythmia agent, antihypertensive agent, and sympathomimetic agent. It belongs to the ethanolamine, propanolamine, secondary amino, ether, monocarboxylic acid amide, and aromatic amide classes. It is the conjugate base of acebutylpyrrolizumab (1+). It is a cardiac-selective β-adrenergic antagonist with minimal effect on bronchial receptors. This drug has a stabilizing effect on heart rhythm and quinidine-like effects, while also possessing a weak intrinsic sympathomimetic effect. Acebutolol is a β-adrenergic blocker. The mechanism of action of acebutylpyrrolizumab is as a β-adrenergic antagonist. Acebutolol is a cardiac-selective β-receptor blocker used to treat hypertension, angina pectoris, and arrhythmias. Acetaminophen has been associated with several clinically significant cases of drug-induced liver injury. Acetaminophen is a synthetic butyrylanilide derivative with antihypertensive and antiarrhythmic effects. It is a cardiac-selective β-adrenergic antagonist with minimal effect on bronchial receptors and intrinsic sympathomimetic properties. Acetaminophen has a stabilizing effect on heart rhythm and is used to treat ventricular arrhythmias, similar to quinidine. Other indications include hypertension, and it can be used alone or in combination with other drugs. Acetaminophen is a cardiac-selective β1-adrenergic antagonist with minimal effect on bronchial receptors. It has a stabilizing effect on heart rhythm and is similar to quinidine, while also having a weak sympathomimetic effect. See also: Acetaminophen hydrochloride (in salt form); diacetylethanolamine (in subclasses); secladex (its active ingredient). Indications: For the treatment of hypertension and premature ventricular contractions in adults. Mechanism of Action Acetaminophen is a selective β1 receptor antagonist. Adrenaline activates β1 receptors, increasing heart rate and blood pressure, and causing the heart to consume more oxygen. Acetaminophen blocks these receptors, thereby lowering heart rate and blood pressure. Therefore, this drug has an effect opposite to adrenaline. Furthermore, β-blockers inhibit the release of renin, a hormone produced by the kidneys that causes vasoconstriction. Pharmacodynamics Acetaminophen is a cardiac-selective β-adrenergic receptor blocker with mild intrinsic sympathomimetic activity (ISA) within its therapeutic dose range. Generally, β-blockers reduce the workload of the heart, making its beating more regular. Compared to non-selective β-blockers, acebutaminophen has a weaker antagonistic effect on peripheral vascular β2 receptors at rest and after adrenaline stimulation. Low-dose acebutaminophen causes milder bronchoconstriction symptoms than non-selective drugs such as propranolol, but more severe than atenolol.

C18H28N2O4

336.43

336.204

37517-30-9

Acebutolol hydrochloride;34381-68-5;Acebutolol-d7;Acebutolol-d5;1189500-68-2

1978

Typically exists as solid at room temperature

1.1±0.1 g/cm3

564.1±50.0 °C at 760 mmHg

119-123ºC

295.0±30.1 °C

0.0±1.6 mmHg at 25°C

1.543

1.95

3

5

10

24

401

0

CCCC(NC1=CC(C(C)=O)=C(OCC(O)CNC(C)C)C=C1)=O

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)

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

Acetobutolol Neptal Acebutolol Sectral Dl-Acebutolol Prent

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)