acebutolol

Acebutolol is an orally active β1 adrenergic receptor (β1AR) antagonist. Acebutolol is used for hypertension, angina pectoris and cardiac arrhythmias research[1][2][3].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

β1 adrenoceptor

Acebutolol is a beta blocker for the treatment of hypertension and arrhythmias. Acebutolol following single intravenous administration (10 mg/kg) to rat results in the plasma clearance of 61.9 mL/min/kg, the volume of distribution of 9.6 L/kg, and an elimination half-life of 1.8 hours. Acebutolol following single intravenous administration (50 mg/kg) to rat results in the plasma clearance of 46.5 mL/min/kg, the volume of distribution of 9.5 L/kg, and an elimination half-life of 2.3 hours[1]. Acebutolol (30 mg/kg) decreases cardiac output by 65% and 31% after 1 min and 10 min measurements, respectively, in Sprague-Dawley rats. Acebutolol (30 mg/kg) significantly reduces regional blood flow (RBF) in most organs either after 1 min or 10 min measurements when compare with the baseline values in Sprague-Dawley rats[3].

[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.

MOLECULAR FORMULA :

C18-H28-N2-O4

MOLECULAR WEIGHT :

336.48

WISWESSER LINE NOTATION :

3VMR CV1 DO1YQ1MY1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

152 mg/kg

TOXIC EFFECTS :

Cardiac - change in conduction velocity Vascular - BP lowering not characterized in autonomic section

REFERENCE :

JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 20,69,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

137 mg/kg/24D-I

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 111,533,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

109 mg/kg/22D-I

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 111,533,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

125 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CKFRAY Ceskoslovenska Farmacie. (PNS-Ustredni Expedice a Dovoz Tisku, Kafkova 19, 160 00 Prague 6, Czechoslovakia) V.1- 1952- Volume(issue)/page/year: 42,82,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

75200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NPMDAD Nouvelle Presse Medicale. (Paris, France) V.1-11, 1972-82. Volume(issue)/page/year: 7,3258,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section Kidney, Ureter, Bladder - changes in blood vessels or in circulation of kidney

REFERENCE :

MASODV Masui to Sosei. Anesthesia and Resuscitation. (Hiroshima Masui Igakkai, Hiroshima Daigaku Igakubu Masuigaku Kyoshitsu, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan) V.6- 1970- Volume(issue)/page/year: 16,13,1980 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

120 mg/kg

SEX/DURATION :

female 34-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - respiratory system

REFERENCE :

DPTHDL Developmental Pharmacology and Therapeutics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 4(Suppl 1),109,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1080 mg/kg

SEX/DURATION :

female 1-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - biochemical and metabolic

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 283,1077,1981