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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
Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.
1991 Oct
[Particular features of the impact of certain vegetotropic drugs on the excitability of cholinergic structures, contractile myocardial function and electromotive stomach activity].
2005
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
Decreased microvascular nitric oxide-dependent vasodilation in postural tachycardia syndrome.
2005 Oct 25
Effect of defocused CO2 laser on equine tissue perfusion.
2006
The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans.
2006 Aug 1
Noradrenergic and cholinergic neural pathways mediate stress-induced reactivation of colitis in the rat.
2006 Jan 30
Different vascular responses in glabrous and nonglabrous skin with increasing core temperature during exercise.
2006 Jul
Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats.
2006 Jul
Ventricular tachyarrhythmias (out of hospital cardiac arrests).
2006 Jun
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
Refractory Electrical Storm suppression by bretylium.
2006 Nov 18
LC/MS/MS analysis of quaternary ammonium drugs and herbicides in whole blood.
2006 Oct 2
Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines.
2006 Sep
Modification of cutaneous vasodilator response to heat stress by daytime exogenous melatonin administration.
2006 Sep
Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers.
2007
Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.
2007 Aug
Cholinergic innervation of the guinea-pig isolated vas deferens.
2007 Dec
Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.
2007 Dec
Reducing myocardial injury by minimizing imbalance between oxygen supply and demand.
2007 Jul
Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.
2007 Jul
The effect of the sympathetic and sensory nervous system on active eustachian tube function in the rat.
2007 Mar
Pharmacotherapy options for complex regional pain syndrome.
2007 May
[Electrical storm].
2007 Nov
Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice.
2007 Sep
Successful catheter ablation of persistent electrical storm late post myocardial infarction by targeting purkinje arborization triggers.
2008
Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome.
2008
Prediction of oral absorption in humans by experimental immobilized artificial membrane chromatography indices and physicochemical descriptors.
2008 Aug 6
Bretylium abolishes neurotransmitter release without necessarily abolishing the nerve terminal action potential in sympathetic terminals.
2008 Feb
Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome.
2008 Jan
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
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
Neural reflex hypotension induced by very small dose of hypertonic NaCl solution in rats.
2009 Feb 28
The involvement of heating rate and vasoconstrictor nerves in the cutaneous vasodilator response to skin warming.
2009 Jan
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
Arrhythmia and acute coronary syndrome suppression and cardiac resuscitation management with bretylium.
2009 Nov-Dec
[Recurrent refractory ventricular fibrillation: how many times is it necessary to defibrillate?].
2010 Apr
Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia.
2010 Aug 9
Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue.
2010 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
Increased excitability and spontaneous activity of rat sensory neurons following in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root ganglion.
2010 Nov
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