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Identification
Name Bretylium
Accession Number DB01158 (APRD00830)
Type small molecule
Groups approved
Description

Bretylium blocks the release of noradrenaline from the peripheral sympathetic nervous system, and is used in emergency medicine, cardiology, and other specialties for the acute management of ventricular tachycardia and ventricular fibrillation. The primary mode of action for bretylium is thought to be inhibition of voltage-gated K(+) channels. Recent evidence has shown that bretylium may also inhibit the Na,K-ATPase by binding to the extracellular K-site.
Structure Thumb
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Display: 2D Structure | 3D Structure
Synonyms
Bretylate
Bretylium tolsylate
Bretylium tosylate
Bretylum
Salts Not Available
Brand names
Name Company
Bretylan
Bretylol
Darenthin
Darentin
Ornid
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Anti-Arrhythmia Agents
  • Adrenergic Antagonists
CAS number 59-41-6
Weight Average: 243.163
Monoisotopic: 242.054437196
Chemical Formula C11H17BrN
InChI Key InChIKey=AAQOQKQBGPPFNS-UHFFFAOYSA-N
InChI
InChI=1S/C11H17BrN/c1-4-13(2,3)9-10-7-5-6-8-11(10)12/h5-8H,4,9H2,1-3H3/q+1
Plain Text
IUPAC Name
[(2-bromophenyl)methyl](ethyl)dimethylazanium
SMILES
CC[N+](C)(C)CC1=CC=CC=C1Br
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
Substructures
  • Benzene and Derivatives
  • Aryl Halides
  • Quaternary Ammonium Salts
  • Aromatic compounds
  • Halobenzenes
  • Cations
Pharmacology
Indication For use in the prophylaxis and therapy of ventricular fibrillation. Also used in the treatment of life-threatening ventricular arrhythmias, such as ventricular tachycardia, that have failed to respond to adequate doses of a first-line antiarrhythmic agent, such as lidocaine.
Pharmacodynamics Bretylium is a bromobenzyl quaternary ammonium compound which selectively accumulates in sympathetic ganglia and their postganglionic adrenergic neurons where it inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. Bretylium also suppresses ventricular fibrillation and ventricular arrhythmias.
Mechanism of action Bretylium inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. The mechanisms of the antifibrillatory and antiarrhythmic actions of bretylium are not established. In efforts to define these mechanisms, the following electrophysiologic actions of bretylium have been demonstrated in animal experiments: increase in ventricular fibrillation threshold, increase in action potential duration and effective refractory period without changes in heart rate, little effect on the rate of rise or amplitude of the cardiac action potential (Phase 0) or in resting membrane potential (Phase 4) in normal myocardium, decrease in the disparity in action potential duration between normal and infarcted regions, and increase in impulse formation and spontaneous firing rate of pacemaker tissue as well as increase ventricular conduction velocity.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism No metabolites have been identified following administration in man and laboratory animals.
Route of elimination Not Available
Half life The terminal half-life in four normal volunteers averaged 7.8±0.6 hours (range 6.9-8.1). During hemodialysis, this patient's arterial and venous bretylium concentrations declined rapidly, resulting in a half-life of 13 hours.
Clearance Not Available
Toxicity Oral, mouse: LD50 = 400 mg/kg. In the presence of life-threatening arrhythmias, underdosing with bretylium probably presents a greater risk to the patient than potential overdosage. However, one case of accidental overdose has been reported in which a rapidly injected intravenous bolus of 30 mg/kg was given instead of an intended 10 mg/kg dose during an episode of ventricular tachycardia. Marked hypertension resulted, followed by protracted refractory hypotension. The patient expired 18 hours later in asystole, complicated by renal failure and aspiration pneumonitis. Bretylium serum levels were 8000 ng/mL.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abraxis pharmaceutical products
  • Astrazeneca lp
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • International medication system
  • Luitpold pharmaceuticals inc
  • Abbott laboratories pharmaceutical products div
  • B braun medical inc
  • Baxter healthcare corp
Packagers Not Available
Dosage forms
Form Route Strength
Liquid Intramuscular
Solution Intramuscular
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility Freely soluble Not Available
Predicted Properties
Property Value Source
water solubility 1.54e-04 g/l ALOGPS
logP -1.4 ALOGPS
logP -1.1 ChemAxon
logS -6.3 ALOGPS
pKa (strongest acidic) 17.58 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 0 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 0 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 72.89 ChemAxon
polarizability 23.24 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00645 Link_out
PubChem Compound 2431 Link_out
PubChem Substance 46505320 Link_out
ChemSpider 2337 Link_out
ChEBI 3172 Link_out
ChEMBL 3172 Link_out
Therapeutic Targets Database DAP000939 Link_out
PharmGKB PA448662 Link_out
Drug Product Database 2185377 Link_out
RxList http://www.rxlist.com/cgi/generic3/bretosy.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Bretylium Link_out
ATC Codes
  • C01BD02
AHFS Codes
  • 24:04.04.20
PDB Entries Not Available
FDA label Not Available
MSDS show (73 KB)
Interactions
Drug Interactions
Drug Interaction
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arryhthmias
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
Ranolazine Possible additive effect on QT prolongation
Telithromycin Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Food Interactions Not Available
Targets

1. Sodium/potassium-transporting ATPase alpha-1 chain

Pharmacological action: yes
Actions: inhibitor

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients

Organism class: human
UniProt ID: P05023 Link_out
Gene: ATP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dzimiri N, Almotrefi AA: Inhibition of myocardial Na()-K()-ATPase activity by bretylium: role of potassium. Arch Int Pharmacodyn Ther. 1992 Jul-Aug;318:76-85. Pubmed
  2. Helms JB, Arnett KL, Gatto C, Milanick MA: Bretylium, an organic quaternary amine, inhibits the Na,K-ATPase by binding to the extracellular K-site. Blood Cells Mol Dis. 2004 May-Jun;32(3):394-400. Pubmed
  3. Dzimiri N, Almotrefi AA: Interaction of bretylium tosylate with guinea-pig myocardial Na()-K()-ATPase. Gen Pharmacol. 1991;22(5):935-8. Pubmed
  4. Tiku PE, Nowell PT: Selective inhibition of K(+)-stimulation of Na,K-ATPase by bretylium. Br J Pharmacol. 1991 Dec;104(4):895-900. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19