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Details

Stereochemistry ACHIRAL
Molecular Formula C11H17BrN
Molecular Weight 243.1633
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of BRETYLIUM

SMILES

CC[N+](C)(C)Cc1ccccc1Br

InChI

InChIKey=AAQOQKQBGPPFNS-UHFFFAOYSA-N
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

HIDE SMILES / InChI
Bretylium (bretylium tosylate) is an antifibrillatory and antiarrhythmic agent. Bretylium is abromobenzyl 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. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission. The drug is poorly absorbed orally, requiring either i.m. or i.v. administration.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.5 mM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BRETYLIUM TOSYLATE

Approved Use

Bretylium (bretylium tosylate injection ) Tosylate is indicated in the prophylaxis and therapy of ventricular fibrillation. Bretylium (bretylium tosylate injection ) tosylate is also indicated 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. Use of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION should be limited to intensive care units, coronary care units or other facilities where equipment and personnel for constant monitoring of cardiac arrhythmias and blood pressure are available. Following injection of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION there may be a delay of 20 minutes to 2 hours in the onset of antiarrhythmic action, although it appears to act within minutes in ventricular fibrillation. The delay in effect appears to be longer after intramuscular than after intravenous injection.
Primary
BRETYLIUM TOSYLATE

Approved Use

Bretylium (bretylium tosylate injection ) Tosylate is indicated in the prophylaxis and therapy of ventricular fibrillation. Bretylium (bretylium tosylate injection ) tosylate is also indicated 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. Use of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION should be limited to intensive care units, coronary care units or other facilities where equipment and personnel for constant monitoring of cardiac arrhythmias and blood pressure are available. Following injection of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION there may be a delay of 20 minutes to 2 hours in the onset of antiarrhythmic action, although it appears to act within minutes in ventricular fibrillation. The delay in effect appears to be longer after intramuscular than after intravenous injection.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1100 ng/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BRETYLIUM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
535 min
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BRETYLIUM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Other AEs: Hypotension, Heart block...
Other AEs:
Hypotension (32%)
Heart block (4%)
Congestive heart failure (5%)
Proarrhythmia (3%)
Nausea (6%)
Confusion (4%)
Thrombocytopenia (3%)
Fever (1%)
Diarrhea (5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fever 1%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Proarrhythmia 3%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Thrombocytopenia 3%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Hypotension 32%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Confusion 4%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Heart block 4%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Congestive heart failure 5%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Diarrhea 5%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Nausea 6%
2500 mg multiple, intravenous
Dose: 2500 mg
Route: intravenous
Route: multiple
Dose: 2500 mg
Sources:
unhealthy, 66±12 years
n = 103
Health Status: unhealthy
Age Group: 66±12 years
Sex: M+F
Population Size: 103
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
An increase in extracellular Ca(2+) concentration induces pigment aggregation in teleostean melanophores.
2002 Aug
Localized abdominal pain following sympathetic blockade with bretylium for the management of complex regional pain syndrome.
2002 Feb
Regional variation in electrically-evoked contractions of rabbit isolated pulmonary artery.
2002 Oct
Potentially significant drug interactions of class III antiarrhythmic drugs.
2003
How do Belgian mobile intensive care units deal with cardiovascular emergencies?
2003 Jun
Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day.
2003 Mar
Delayed distribution of active vasodilation and altered vascular conductance in aged skin.
2003 Mar
Cutaneous active vasodilation in humans during passive heating postexercise.
2003 Sep
Effects of reboxetine on sympathetic neuroeffector transmission in rabbit carotid artery.
2003 Sep
Altered neurotransmitter control of reflex vasoconstriction in aged human skin.
2004 Jul 15
Bretylium, an organic quaternary amine, inhibits the Na,K-ATPase by binding to the extracellular K-site.
2004 May-Jun
Nicotine increases initial blood flow responses to local heating of human non-glabrous skin.
2004 Sep 15
Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease?
2004 Sep-Oct
[Particular features of the impact of certain vegetotropic drugs on the excitability of cholinergic structures, contractile myocardial function and electromotive stomach activity].
2005
Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling.
2005 Apr
Exogenous melatonin delays gastric emptying rate in rats: role of CCK2 and 5-HT3 receptors.
2005 Dec
Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options.
2005 Jan 1
Complex regional pain syndrome: which treatments show promise?
2005 Jul
Active cutaneous vasodilation in resting humans during mild heat stress.
2005 Mar
Ca2+ sensitization and the regulation of contractility in rat anococcygeus and retractor penis muscle.
2005 May 15
Solute attributes and molecular interactions contributing to "U-shape" retention on a fluorinated high-performance liquid chromatography stationary phase.
2005 May 6
Peripheral mechanisms involved in gastric mucosal protection by intracerebroventricular and intraperitoneal nociceptin in rats.
2005 Sep
Effect of defocused CO2 laser on equine tissue perfusion.
2006
Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals.
2006 Aug
Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus.
2006 Feb
Different vascular responses in glabrous and nonglabrous skin with increasing core temperature during exercise.
2006 Jul
Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats.
2006 Mar
Nitric oxide and noradrenaline contribute to the temperature threshold of the axon reflex response to gradual local heating in human skin.
2006 May 1
LC/MS/MS analysis of quaternary ammonium drugs and herbicides in whole blood.
2006 Oct 2
Modification of cutaneous vasodilator response to heat stress by daytime exogenous melatonin administration.
2006 Sep
Cholinergic innervation of the guinea-pig isolated vas deferens.
2007 Dec
Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.
2007 Jul
[Electrical storm].
2007 Nov
Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice.
2007 Sep
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.
2008
Bretylium abolishes neurotransmitter release without necessarily abolishing the nerve terminal action potential in sympathetic terminals.
2008 Feb
Influence of intravesicular pH drift and membrane binding on the liposomal release of a model amine-containing permeant.
2008 Jan
The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans.
2008 Jul
Anti-arrhythmic and vasopressor medications for the treatment of ventricular fibrillation in severe hypothermia: a systematic review of the literature.
2008 Jul
EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy.
2008 May
Nervous and humoral control of cardiac performance in the winter flounder (Pleuronectes americanus).
2009 Apr
Plasma hyperosmolality elevates the internal temperature threshold for active thermoregulatory vasodilation during heat stress in humans.
2009 Dec
Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise.
2009 Dec 15
The diagnosis of brain death.
2009 Jan-Mar
Investigation of the role of adrenergic and non-nitrergic, non-adrenergic neurotransmission in the sheep isolated internal anal sphincter.
2009 Mar
A resuscitation of bretylium?
2009 Nov-Dec
Survival after prolonged resuscitation with 99 defibrillations due to Torsade De Pointes cardiac electrical storm: a case report.
2010 Feb 6
Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age.
2010 Jul
Nervous and humoral catecholaminergic control of blood pressure and cardiac performance in the Antarctic fish Pagothenia borchgrevinki.
2010 Jun
Evidence based guidelines for complex regional pain syndrome type 1.
2010 Mar 31
Patents

Sample Use Guides

In Vivo Use Guide
BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION is to be used clinically only for treatment of life-threatening ventricular arrhythmias under constant electrocardiographic monitoring. The clinical use of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION is for short-term use only. Patients should either be kept supine during the course of bretylium (bretylium tosylate injection ) therapy or be closely observed for postural hypotension. The optimal dose schedule for parenteral administration of the drug has not been determined. There is comparatively little experience with dosages greater than 40mg/kg/day, although such doses have been used without apparent adverse effects. The following schedules are suggested: A. For immediately Life-threatening Ventricular Arrhythmias such as Ventricular Fibrillation or Hemodynamically Unstable Ventricular Tachycardia: Administer undiluted BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION at a dosage of 5mg/kg of body weight by rapid intravenous injection. Other usual cardiopulmonary resuscitative procedures, including electrical cardioversion, should be employed prior to and following the injection in accordance with good medical practice. If ventricular fibrillation persists, the dosage may be increased to 10mg/kg and repeated as necessary. For continuous suppression, dilute Bretylium (bretylium tosylate injection ) Tosylate Injection with Dextrose Injection, USP or Sodium Chloride Injection, USP using the table below and administer the diluted solution as a constant infusion of 1 to 2mg Bretylium (bretylium tosylate injection ) Tosylate Injection per minute, (see Table below). When administering Bretylium (bretylium tosylate injection ) Tosylate Injection (or any potent medication) by continuous intravenous infusion, it is advisable to use a precision volume control device. An alternative maintenance schedule is to infuse the diluted solution at a dosage of 5 to 10mg Bretylium (bretylium tosylate injection ) Tosylate per kg body weight, over a period greater than 8 minutes, every 6 hours. More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension. B. Other ventricular arrhythmias: 1) Intravenous Use: Bretylium (bretylium tosylate injection ) tosylate injection must be diluted as described above before intravenous use. Administer the diluted solution at a dosage of 5 to 10mg bretylium (bretylium tosylate injection ) tosylate per kg of body weight by intravenous infusion over a period greater than 8 minutes. More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension. Subsequent doses may be given at 1 to 2 hour intervals if the arrhythmia persists. 2) For Intramuscular Injection: DO NOT DILUTE BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION PRIOR TO INTRAMUSCULAR INJECTION. Inject 5 to 10mg bretylium (bretylium tosylate injection ) tosylate per kg of body weight. Subsequent doses may be given at 1 to 2 hour intervals if the arrhythmia persists. Thereafter, maintain the same dosage every 6 to 8 hours. Intramuscular injection should not be made directly into or near a major nerve, and the site of injection should be varied on repeated injection. Not more than 5mL should be injected intramuscularly in one site. (See PRECAUTONS) As soon as possible, and when indicated, patients should be changed to an oral antiarrhythmic agent for maintenance therapy.
Route of Administration: Other
bretylium at 1-100 uM prolonged the action potentials of the Wistar Kyoto normotensive rat left ventricular strip.
Name Type Language
BRETYLIUM
VANDF   WHO-DD  
Common Name English
(O-BROMOBENZYL)ETHYLDIMETHYLAMMONIUM
Common Name English
BRETYLIUM [WHO-DD]
Common Name English
BRETYLIUM [VANDF]
Common Name English
BRETYLIUM ION
Common Name English
BENZENEMETHANAMINIUM, 2-BROMO-N-ETHYL-N,N-DIMETHYL-
Systematic Name English
BRETYLIUM CATION
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29713
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
Code System Code Type Description
EPA CompTox
59-41-6
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
DRUG CENTRAL
394
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
WIKIPEDIA
BRETYLIUM
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
FDA UNII
RZR75EQ2KJ
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
RXCUI
19685
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C77300
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
MESH
C045166
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
LACTMED
Bretylium
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
IUPHAR
7130
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
EVMPD
SUB00867MIG
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
DRUG BANK
DB01158
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
PUBCHEM
2431
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY
CAS
59-41-6
Created by admin on Sat Jun 26 16:40:45 UTC 2021 , Edited by admin on Sat Jun 26 16:40:45 UTC 2021
PRIMARY