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Details

Stereochemistry ACHIRAL
Molecular Formula C11H17BrN.C7H7O3S
Molecular Weight 414.357
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BRETYLIUM TOSYLATE

SMILES

CC1=CC=C(C=C1)S([O-])(=O)=O.CC[N+](C)(C)CC2=C(Br)C=CC=C2

InChI

InChIKey=KVWNWTZZBKCOPM-UHFFFAOYSA-M
InChI=1S/C11H17BrN.C7H8O3S/c1-4-13(2,3)9-10-7-5-6-8-11(10)12;1-6-2-4-7(5-3-6)11(8,9)10/h5-8H,4,9H2,1-3H3;2-5H,1H3,(H,8,9,10)/q+1;/p-1

HIDE SMILES / InChI

Molecular Formula C11H17BrN
Molecular Weight 243.163
Charge 1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C7H7O3S
Molecular Weight 171.194
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.
2001 Apr
Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress.
2001 Aug
Acute cold exposure induces vagally mediated Fos expression in gastric myenteric neurons in conscious rats.
2001 Aug
Dependence of reversed-phase retention of ionizable analytes on pH, concentration of organic solvent and silanol activity.
2001 Aug 3
Bretylium or 6-OHDA-resistant, action potential-evoked Ca2+ transients in varicosities of the mouse vas deferens.
2002 Apr
Bretylium or 6-OHDA-resistant, action potential-evoked Ca2+ transients in varicosities of the mouse vas deferens: commentary on Jackson and Cunnane.
2002 Apr
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
Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms.
2002 Jan 15
Action potential duration restitution and ventricular fibrillation due to rapid focal excitation.
2002 May
Regional variation in electrically-evoked contractions of rabbit isolated pulmonary artery.
2002 Oct
Potentially significant drug interactions of class III antiarrhythmic drugs.
2003
Survival and normal neurological outcome after CPR with periodic Gz acceleration and vasopressin.
2003 Feb
How do Belgian mobile intensive care units deal with cardiovascular emergencies?
2003 Jun
Bretylium, an organic quaternary amine, inhibits the Na,K-ATPase by binding to the extracellular K-site.
2004 May-Jun
Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans.
2004 Nov
[Particular features of the impact of certain vegetotropic drugs on the excitability of cholinergic structures, contractile myocardial function and electromotive stomach activity].
2005
Cholinergic innervation of the mouse isolated vas deferens.
2005 Dec
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
The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans.
2006 Aug 1
Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin.
2006 Jan
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
Refractory Electrical Storm suppression by bretylium.
2006 Nov 18
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
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
Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome.
2008 Jan
The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans.
2008 Jul
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 involvement of heating rate and vasoconstrictor nerves in the cutaneous vasodilator response to skin warming.
2009 Jan
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
[Recurrent refractory ventricular fibrillation: how many times is it necessary to defibrillate?].
2010 Apr
Tetrahydrobiopterin does not affect end-organ responsiveness to norepinephrine-mediated vasoconstriction in aged skin.
2010 Dec
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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 14:58:13 GMT 2023
Edited
by admin
on Fri Dec 15 14:58:13 GMT 2023
Record UNII
78ZP3YR353
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRETYLIUM TOSYLATE
MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
USAN  
Official Name English
BRETYLIUM TOSILATE [MART.]
Common Name English
BENZENEMETHANAMINIUM, 2-BROMO-N-ETHYL-N,N-DIMETHYL-, SALT WITH 4-METHYLBENZENESULFONIC ACID (1:1)
Common Name English
BRETYLIUM TOSYLATE [USAN]
Common Name English
bretylium tosilate [INN]
Common Name English
(O-BROMOBENZYL)ETHYLDIMETHYLAMMONIUM P-TOLUENESULPHONATE
Common Name English
BRETYLIUM TOSYLATE [ORANGE BOOK]
Common Name English
BRETYLIUM TOSYLATE [USP-RS]
Common Name English
NSC-62164
Code English
BRETYLIUM TOSYLATE [USP MONOGRAPH]
Common Name English
BRETYLOL
Brand Name English
BRETYLIUM TOSILATE
INN   MART.   WHO-DD  
INN  
Official Name English
Bretylium tosilate [WHO-DD]
Common Name English
ASL-603
Code English
BRETYLIUM TOSYLATE [MI]
Common Name English
(O-BROMOBENZYL)ETHYLDIMETHYLAMMONIUM P-TOLUENESULFONATE
Common Name English
BRETYLIUM TOSYLATE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-VATC QC01BD02
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
NCI_THESAURUS C29713
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
WHO-ATC C01BD02
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
Code System Code Type Description
EVMPD
SUB05887MIG
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
NCI_THESAURUS
C47418
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
PUBCHEM
6100
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
CHEBI
3173
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
INN
927
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
DRUG BANK
DBSALT001050
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
RS_ITEM_NUM
1076352
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
MERCK INDEX
m2647
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY Merck Index
CAS
61-75-6
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
SMS_ID
100000088661
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
ChEMBL
CHEMBL1199080
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
NSC
62164
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
ECHA (EC/EINECS)
200-516-8
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
FDA UNII
78ZP3YR353
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
EPA CompTox
DTXSID1022685
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
MESH
D001950
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY
RXCUI
1737
Created by admin on Fri Dec 15 14:58:13 GMT 2023 , Edited by admin on Fri Dec 15 14:58:13 GMT 2023
PRIMARY RxNorm
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY