Amiodarone

Amiodarone is an antiarrhythmic drug for inhibition of ATP-sensitive potassium channel with IC50 of 19.1 μM. Target: Potassium ChannelAmiodarone shows beta blocker-like and potassium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. Amiodarone (2-butyl, 3-(4-diethylaminoethoxy, 3,5-diiodo, benzoyl) benzofuran hydrochloride), an anti-anginal drug which causes coronary dilatation and depresses myocardial oxygen consumption, was found to protect anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation.2. A 5% (73.4 mM) solution of amiodarone had no local anaesthetic action on guinea-pig skin [1]. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect [2].

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Cardiovascular Disease

[1]. Singh, B.N. and E.M. Vaughan Williams, The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol, 1970. 39(4): p. 657-67.

[2]. Rosenbaum, M.B., et al., Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol, 1976. 38(7): p. 934-44.

Nigericin sodium salt | Senicapoc | E-4031 | 4-AMINOPYRIDINE | Ginsenoside Rg3 | TRAM-34 | Dofetilide | PAP-1 | Minoxidil | Flufenamic Acid | Flupirtine maleate | NS-1619 | Endoxifen (Z-isomer hydrochloride) | NS309 | Quinine

DATA ITEMS CITED :

15

MOLECULAR FORMULA :

C25-H29-I2-N-O3

MOLECULAR WEIGHT :

645.35

WISWESSER LINE NOTATION :

T56 BOJ C4 DVR CI EI DO2N2&2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1714 mg/kg/21W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - cough Lungs, Thorax, or Respiration - cyanosis Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 308,779,1983

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

568 mg/kg/9W-I

TOXIC EFFECTS :

Cardiac - pulse rate Liver - fatty liver degeneration

REFERENCE :

JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 107,967,1985

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1869 mg/kg/22W-I

TOXIC EFFECTS :

Behavioral - coma Vascular - BP lowering not characterized in autonomic section Endocrine - evidence of thyroid hypofunction

REFERENCE :

AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 77,751,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

416 mg/kg/30D-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

REFERENCE :

AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 147,50,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

133 mg/kg/23D-I

TOXIC EFFECTS :

Skin and Appendages - photosensitivity (after systemic exposure)

REFERENCE :

LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,51,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3651 mg/kg/2.3Y-I

TOXIC EFFECTS :

Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring) Liver - liver function tests impaired Liver - multiple effects

REFERENCE :

AJGAAR American Journal of Gastroenterology. (American College of Gastroenterology, Inc., 428 E. Preston St., Baltimore, MD 21202) V.21- 1954- Volume(issue)/page/year: 83,161,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

36 mg/kg/1D-I

TOXIC EFFECTS :

Endocrine - evidence of thyroid hyperfunction

REFERENCE :

IJMDAI Israel Journal of Medical Sciences. (POB 1435, Jerusalem 91013, Israel) V.1- 1965- Volume(issue)/page/year: 21,165,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

26 mg/kg/1D-C

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Cardiac - EKG changes not diagnostic of specified effects

REFERENCE :

AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 131,1214,1996

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

57 mg/kg/5D-I

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 97,561,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

48 mg/kg/3D-I

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

REFERENCE :

AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 130,399,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Multiple routes

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1475 mg/kg/7W-I

TOXIC EFFECTS :

Cardiac - other changes

REFERENCE :

AJCDAG American Journal of Cardiology. (Technical Pub. Co., 875 Third Ave., New York, NY 10022) V.1- 1958- Volume(issue)/page/year: 58,1110,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

885 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #0076973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #0076973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

254 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EJTXAZ European Journal of Toxicology and Environmental Hygiene. (Paris, France) V.7-9, 1974-76. For publisher information, see TOERD9. Volume(issue)/page/year: 8,122,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

178 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EJTXAZ European Journal of Toxicology and Environmental Hygiene. (Paris, France) V.7-9, 1974-76. For publisher information, see TOERD9. Volume(issue)/page/year: 8,188,1975