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
Synonyms
  • (2-Bromobenzyl)ethyldimethylaminium
  • 2-Bromo-N-ethyl-N,N-dimethylbenzenemethanaminium
  • N-Ethyl-N,N-dimethyl-2-bromobenzenemethanaminium
Product Ingredients
IngredientUNIICASInChI Key
Bretylium tosylate78ZP3YR35361-75-6KVWNWTZZBKCOPM-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bretylate Inj 50mg/mlLiquid50 mgIntramuscular; IntravenousGlaxo Wellcome1980-12-312000-01-19Canada
Bretylium Tosylate Inj 50mg/mlSolution50 mgIntramuscular; IntravenousAbbott1991-12-312007-07-31Canada
Bretylium Tosylate Injection USPSolution50 mgIntramuscular; IntravenousSandoz Canada Incorporated1995-12-31Not applicableCanada
International/Other Brands
Anxyrex (Sanofi-Aventis) / Bretylol (ICI) / Bromidem (Nycomed) / Creosedin (AstraZeneca) / Darenthin (Burroughs Wellcome) / Lexotan (Roche) / Xionil (Novartis)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Bretylium Tosylate 0.2% and Dextrose 5% InjBretylium tosylate (2 mg) + Glucose (50 mg)SolutionIntravenousAbbott1988-12-312007-07-31Canada
Bretylium Tosylate 0.4% and Dextrose 5% InjBretylium tosylate (4 mg) + Glucose (50 mg)SolutionIntravenousAbbott1988-12-312007-07-31Canada
Categories
UNII
RZR75EQ2KJ
CAS number
59-41-6
Weight
Average: 243.163
Monoisotopic: 242.054437196
Chemical Formula
C11H17BrN
InChI Key
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
IUPAC Name
[(2-bromophenyl)methyl](ethyl)dimethylazanium
SMILES
CC[N+](C)(C)CC1=CC=CC=C1Br

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.

Structured Indications
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.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1
inhibitor
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Bretylium.Experimental
AcebutololBretylium may increase the bradycardic activities of Acebutolol.Approved
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Bretylium.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Bretylium.Approved, Investigational
AliskirenThe risk or severity of adverse effects can be increased when Bretylium is combined with Aliskiren.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Bretylium.Approved, Withdrawn
AmbrisentanBretylium may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineBretylium may increase the hypotensive activities of Amifostine.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Bretylium.Approved
AmiodaroneBretylium may increase the bradycardic activities of Amiodarone.Approved, Investigational
AmlodipineThe risk or severity of adverse effects can be increased when Amlodipine is combined with Bretylium.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Bretylium.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Bretylium.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Bretylium is combined with Amyl Nitrite.Approved
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Bretylium.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Apraclonidine is combined with Bretylium.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Bretylium.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Bretylium.Approved
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Bretylium.Approved, Investigational
AtenololBretylium may increase the bradycardic activities of Atenolol.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Bretylium is combined with Azilsartan medoxomil.Approved
BarbexacloneBarbexaclone may increase the hypotensive activities of Bretylium.Experimental
BarbitalBarbital may increase the hypotensive activities of Bretylium.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Bretylium.Approved
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Bretylium.Approved, Investigational
BendroflumethiazideBretylium may increase the bradycardic activities of Bendroflumethiazide.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Bretylium.Withdrawn
BepridilBretylium may increase the hypotensive activities of Bepridil.Approved, Withdrawn
BeractantBretylium may increase the bradycardic activities of Beractant.Approved
BetaxololBretylium may increase the bradycardic activities of Betaxolol.Approved
BethanidineBethanidine may increase the hypotensive activities of Bretylium.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Bretylium.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Bretylium.Approved, Investigational
BisoprololBretylium may increase the bradycardic activities of Bisoprolol.Approved
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Bretylium.Approved, Investigational
BosentanBosentan may increase the hypotensive activities of Bretylium.Approved, Investigational
BQ-123Bretylium may increase the hypotensive activities of BQ-123.Investigational
BrimonidineBrimonidine may increase the antihypertensive activities of Bretylium.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Bretylium.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Bretylium.Approved, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Bretylium.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Bretylium.Approved, Investigational
BupranololBretylium may increase the hypotensive activities of Bupranolol.Approved
CadralazineCadralazine may increase the hypotensive activities of Bretylium.Experimental
CafedrineBretylium may increase the hypotensive activities of Cafedrine.Investigational
CalfactantBretylium may increase the bradycardic activities of Calfactant.Approved
CanagliflozinThe risk or severity of adverse effects can be increased when Bretylium is combined with Canagliflozin.Approved
CandesartanThe risk or severity of adverse effects can be increased when Candesartan is combined with Bretylium.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Bretylium.Experimental
CaptoprilThe risk or severity of adverse effects can be increased when Bretylium is combined with Captopril.Approved
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Bretylium.Approved
CaroxazoneCaroxazone may increase the hypotensive activities of Bretylium.Withdrawn
CarteololBretylium may increase the bradycardic activities of Carteolol.Approved
CarvedilolBretylium may increase the bradycardic activities of Carvedilol.Approved, Investigational
CeliprololBretylium may increase the hypotensive activities of Celiprolol.Approved, Investigational
CeritinibBretylium may increase the bradycardic activities of Ceritinib.Approved
ChlorothiazideThe risk or severity of adverse effects can be increased when Chlorothiazide is combined with Bretylium.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Bretylium.Approved, Vet Approved
ChlorthalidoneThe risk or severity of adverse effects can be increased when Chlorthalidone is combined with Bretylium.Approved
CicletanineBretylium may increase the hypotensive activities of Cicletanine.Investigational
CilazaprilThe risk or severity of adverse effects can be increased when Bretylium is combined with Cilazapril.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Bretylium.Approved
ClevidipineThe risk or severity of adverse effects can be increased when Bretylium is combined with Clevidipine.Approved
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Bretylium.Approved, Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Bretylium.Approved, Vet Approved
ClonidineBretylium may increase the bradycardic activities of Clonidine.Approved
CloranololBretylium may increase the hypotensive activities of Cloranolol.Experimental
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Bretylium.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Conivaptan is combined with Bretylium.Approved, Investigational
CrizotinibBretylium may increase the bradycardic activities of Crizotinib.Approved
CryptenamineCryptenamine may increase the hypotensive activities of Bretylium.Approved
CyclopenthiazideBretylium may increase the hypotensive activities of Cyclopenthiazide.Experimental
CyclothiazideCyclothiazide may increase the hypotensive activities of Bretylium.Approved
DapagliflozinThe risk or severity of adverse effects can be increased when Bretylium is combined with Dapagliflozin.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Bretylium.Approved
DelaprilBretylium may increase the hypotensive activities of Delapril.Experimental
DeserpidineBretylium may increase the hypotensive activities of Deserpidine.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Bretylium.Approved
DexmedetomidineBretylium may increase the bradycardic activities of Dexmedetomidine.Approved, Vet Approved
DiazoxideDiazoxide may increase the hypotensive activities of Bretylium.Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Bretylium.Approved
diethylnorspermineBretylium may increase the hypotensive activities of diethylnorspermine.Investigational
DigoxinBretylium may increase the bradycardic activities of Digoxin.Approved
DihydralazineDihydralazine may increase the hypotensive activities of Bretylium.Investigational
DiltiazemBretylium may increase the bradycardic activities of Diltiazem.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Bretylium is combined with Dinutuximab.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Dipyridamole is combined with Bretylium.Approved
DonepezilBretylium may increase the bradycardic activities of Donepezil.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Bretylium.Approved
DoxazosinThe risk or severity of adverse effects can be increased when Doxazosin is combined with Bretylium.Approved
DronedaroneBretylium may increase the bradycardic activities of Dronedarone.Approved
DuloxetineBretylium may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineBretylium may increase the hypotensive activities of Efonidipine.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Bretylium is combined with Empagliflozin.Approved
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Bretylium.Approved, Vet Approved
EnalaprilatBretylium may increase the hypotensive activities of Enalaprilat.Approved
EndralazineEndralazine may increase the hypotensive activities of Bretylium.Experimental
EpanololBretylium may increase the hypotensive activities of Epanolol.Experimental
EplerenoneThe risk or severity of adverse effects can be increased when Eplerenone is combined with Bretylium.Approved
EpoprostenolBretylium may increase the hypotensive activities of Epoprostenol.Approved
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Bretylium.Approved
EsmololBretylium may increase the bradycardic activities of Esmolol.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Etacrynic acid is combined with Bretylium.Approved
FelodipineThe risk or severity of adverse effects can be increased when Felodipine is combined with Bretylium.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Bretylium.Approved
Ferulic acidBretylium may increase the hypotensive activities of Ferulic acid.Experimental
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Bretylium.Approved
FingolimodBretylium may increase the bradycardic activities of Fingolimod.Approved, Investigational
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Bretylium.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Bretylium.Approved, Vet Approved
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Bretylium.Approved, Vet Approved
GalantamineBretylium may increase the bradycardic activities of Galantamine.Approved
GuanabenzGuanabenz may increase the hypotensive activities of Bretylium.Approved
GuanadrelGuanadrel may increase the hypotensive activities of Bretylium.Approved
GuanazodineBretylium may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Bretylium.Approved
GuanfacineBretylium may increase the bradycardic activities of Guanfacine.Approved, Investigational
GuanoclorBretylium may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzBretylium may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanBretylium may increase the hypotensive activities of Guanoxan.Experimental
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Bretylium.Approved, Vet Approved
HarmalineHarmaline may increase the hypotensive activities of Bretylium.Experimental
HexamethoniumBretylium may increase the hypotensive activities of Hexamethonium.Experimental
HexobarbitalHexobarbital may increase the hypotensive activities of Bretylium.Approved
HydracarbazineHydracarbazine may increase the hypotensive activities of Bretylium.Experimental
HydralazineThe risk or severity of adverse effects can be increased when Bretylium is combined with Hydralazine.Approved
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Bretylium.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Bretylium.Approved
IloprostIloprost may increase the hypotensive activities of Bretylium.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Bretylium.Investigational
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Bretylium.Approved
IndapamideThe risk or severity of adverse effects can be increased when Indapamide is combined with Bretylium.Approved
IndenololBretylium may increase the hypotensive activities of Indenolol.Withdrawn
IndoraminIndoramin may increase the hypotensive activities of Bretylium.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Bretylium.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Bretylium.Withdrawn
IrbesartanThe risk or severity of adverse effects can be increased when Irbesartan is combined with Bretylium.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Bretylium.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Bretylium.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Isosorbide Dinitrate is combined with Bretylium.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Isosorbide Mononitrate is combined with Bretylium.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Bretylium is combined with Isoxsuprine.Approved, Withdrawn
IsradipineThe risk or severity of adverse effects can be increased when Isradipine is combined with Bretylium.Approved
IvabradineBretylium may increase the bradycardic activities of Ivabradine.Approved
KetanserinKetanserin may increase the hypotensive activities of Bretylium.Investigational
LabetalolBretylium may increase the bradycardic activities of Labetalol.Approved
LacidipineBretylium may increase the hypotensive activities of Lacidipine.Approved
LanreotideBretylium may increase the bradycardic activities of Lanreotide.Approved
LatanoprostLatanoprost may increase the hypotensive activities of Bretylium.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Bretylium.Approved, Investigational
LevobunololBretylium may increase the bradycardic activities of Levobunolol.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Bretylium.Approved
LevodopaBretylium may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Levosimendan is combined with Bretylium.Approved, Investigational
LinsidomineBretylium may increase the hypotensive activities of Linsidomine.Experimental
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Bretylium.Approved, Investigational
LofexidineBretylium may increase the hypotensive activities of Lofexidine.Approved, Investigational
LosartanThe risk or severity of adverse effects can be increased when Losartan is combined with Bretylium.Approved
LucinactantBretylium may increase the bradycardic activities of Lucinactant.Approved
MacitentanBretylium may increase the hypotensive activities of Macitentan.Approved
ManidipineBretylium may increase the hypotensive activities of Manidipine.Approved
MannitolThe risk or severity of adverse effects can be increased when Mannitol is combined with Bretylium.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Bretylium.Withdrawn
MecamylamineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Bretylium.Approved
MethazolamideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Bretylium.Approved
MethohexitalMethohexital may increase the hypotensive activities of Bretylium.Approved
MethoserpidineBretylium may increase the hypotensive activities of Methoserpidine.Experimental
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Bretylium.Approved
MethyldopaBretylium may increase the bradycardic activities of Methyldopa.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Bretylium.Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Bretylium.Approved, Investigational
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Bretylium.Approved
MetipranololBretylium may increase the bradycardic activities of Metipranolol.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Metolazone is combined with Bretylium.Approved
MetoprololBretylium may increase the bradycardic activities of Metoprolol.Approved, Investigational
MetyrosineBretylium may increase the hypotensive activities of Metyrosine.Approved
MibefradilBretylium may increase the hypotensive activities of Mibefradil.Withdrawn
MinaprineMinaprine may increase the hypotensive activities of Bretylium.Approved
MinoxidilThe risk or severity of adverse effects can be increased when Minoxidil is combined with Bretylium.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Bretylium.Investigational
MoclobemideMoclobemide may increase the hypotensive activities of Bretylium.Approved
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Bretylium.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Bretylium.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Bretylium.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Bretylium.Approved
MuzolimineBretylium may increase the hypotensive activities of Muzolimine.Experimental
NabiloneThe risk or severity of adverse effects can be increased when Nabilone is combined with Bretylium.Approved, Investigational
NadololBretylium may increase the bradycardic activities of Nadolol.Approved
NaftopidilBretylium may increase the hypotensive activities of Naftopidil.Investigational
NebivololBretylium may increase the bradycardic activities of Nebivolol.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Bretylium is combined with Nesiritide.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Bretylium.Withdrawn
NicardipineThe risk or severity of adverse effects can be increased when Nicardipine is combined with Bretylium.Approved
NicorandilNicorandil may increase the hypotensive activities of Bretylium.Approved
NifedipineThe risk or severity of adverse effects can be increased when Nifedipine is combined with Bretylium.Approved
NiguldipineBretylium may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineBretylium may increase the hypotensive activities of Nilvadipine.Approved
NimodipineThe risk or severity of adverse effects can be increased when Nimodipine is combined with Bretylium.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Bretylium.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Bretylium.Approved
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Bretylium.Approved
NitroglycerinThe risk or severity of adverse effects can be increased when Nitroglycerin is combined with Bretylium.Approved, Investigational
NitroprussideThe risk or severity of adverse effects can be increased when Nitroprusside is combined with Bretylium.Approved
ObinutuzumabBretylium may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Bretylium.Withdrawn
OctreotideBretylium may increase the bradycardic activities of Octreotide.Approved, Investigational
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Bretylium.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Bretylium.Investigational
OxprenololBretylium may increase the hypotensive activities of Oxprenolol.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Bretylium.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Papaverine is combined with Bretylium.Approved
PargylinePargyline may increase the hypotensive activities of Bretylium.Approved
PasireotideBretylium may increase the bradycardic activities of Pasireotide.Approved
PenbutololBretylium may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Bretylium.Approved, Vet Approved
PentoliniumPentolinium may increase the hypotensive activities of Bretylium.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Bretylium.Approved, Investigational
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Bretylium.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Bretylium.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Bretylium.Withdrawn
PhenobarbitalPhenobarbital may increase the hypotensive activities of Bretylium.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Bretylium.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Bretylium.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Bretylium.Approved
PinacidilPinacidil may increase the hypotensive activities of Bretylium.Withdrawn
PindololBretylium may increase the bradycardic activities of Pindolol.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Bretylium.Approved
PirlindolePirlindole may increase the hypotensive activities of Bretylium.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Bretylium.Withdrawn
PolythiazideBretylium may increase the hypotensive activities of Polythiazide.Approved
Poractant alfaBretylium may increase the bradycardic activities of Poractant alfa.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Pramipexole is combined with Bretylium.Approved, Investigational
PrazosinThe risk or severity of adverse effects can be increased when Prazosin is combined with Bretylium.Approved
PrimidonePrimidone may increase the hypotensive activities of Bretylium.Approved, Vet Approved
PropafenoneBretylium may increase the bradycardic activities of Propafenone.Approved
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Bretylium.Approved, Investigational, Vet Approved
PropranololBretylium may increase the bradycardic activities of Propranolol.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Bretylium is combined with Quetiapine.Approved
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Bretylium.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Bretylium.Approved
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Bretylium.Approved
RasagilineRasagiline may increase the hypotensive activities of Bretylium.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Bretylium.Approved
RemikirenRemikiren may increase the hypotensive activities of Bretylium.Approved
RescinnamineBretylium may increase the hypotensive activities of Rescinnamine.Approved
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Bretylium.Approved
RilmenidineRilmenidine may increase the hypotensive activities of Bretylium.Investigational
RiociguatThe risk or severity of adverse effects can be increased when Bretylium is combined with Riociguat.Approved
RisperidoneBretylium may increase the hypotensive activities of Risperidone.Approved, Investigational
RituximabBretylium may increase the hypotensive activities of Rituximab.Approved
RivastigmineBretylium may increase the bradycardic activities of Rivastigmine.Approved, Investigational
RopiniroleThe risk or severity of adverse effects can be increased when Ropinirole is combined with Bretylium.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Bretylium.Approved
RotigotineThe risk or severity of adverse effects can be increased when Rotigotine is combined with Bretylium.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bretylium.Approved
SafrazineSafrazine may increase the hypotensive activities of Bretylium.Withdrawn
SaprisartanBretylium may increase the hypotensive activities of Saprisartan.Experimental
SecobarbitalSecobarbital may increase the hypotensive activities of Bretylium.Approved, Vet Approved
SelegilineSelegiline may increase the hypotensive activities of Bretylium.Approved, Investigational, Vet Approved
SelexipagBretylium may increase the hypotensive activities of Selexipag.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Bretylium.Approved, Vet Approved
SildenafilSildenafil may increase the antihypertensive activities of Bretylium.Approved, Investigational
SitaxentanBretylium may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Withdrawn
Sodium NitriteThe risk or severity of adverse effects can be increased when Sodium Nitrite is combined with Bretylium.Approved
SotalolBretylium may increase the bradycardic activities of Sotalol.Approved
SpiraprilBretylium may increase the hypotensive activities of Spirapril.Approved
SpironolactoneThe risk or severity of adverse effects can be increased when Spironolactone is combined with Bretylium.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Streptokinase is combined with Bretylium.Approved
SufentanilBretylium may increase the bradycardic activities of Sufentanil.Approved, Investigational
TadalafilTadalafil may increase the antihypertensive activities of Bretylium.Approved, Investigational
TalinololBretylium may increase the hypotensive activities of Talinolol.Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Tamsulosin is combined with Bretylium.Approved, Investigational
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Bretylium.Approved, Investigational
TemocaprilBretylium may increase the hypotensive activities of Temocapril.Experimental, Investigational
TerazosinThe risk or severity of adverse effects can be increased when Bretylium is combined with Terazosin.Approved
TerlipressinBretylium may increase the hypotensive activities of Terlipressin.Approved, Investigational
TetrahydropalmatineBretylium may increase the hypotensive activities of Tetrahydropalmatine.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Bretylium.Approved, Investigational, Withdrawn
TheodrenalineBretylium may increase the hypotensive activities of Theodrenaline.Investigational
ThiamylalThiamylal may increase the hypotensive activities of Bretylium.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Bretylium.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Bretylium.Withdrawn
TiboloneBretylium may increase the hypotensive activities of Tibolone.Approved
TicrynafenBretylium may increase the hypotensive activities of Ticrynafen.Withdrawn
TimololBretylium may increase the bradycardic activities of Timolol.Approved
TizanidineBretylium may increase the bradycardic activities of Tizanidine.Approved
TolazolineTolazoline may increase the hypotensive activities of Bretylium.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Bretylium.Approved, Withdrawn
TolonidineBretylium may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Bretylium.Approved
TorasemideThe risk or severity of adverse effects can be increased when Torasemide is combined with Bretylium.Approved
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Bretylium.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Bretylium.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Bretylium.Approved
TravoprostTravoprost may increase the hypotensive activities of Bretylium.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Bretylium.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Bretylium.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Triamterene is combined with Bretylium.Approved
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Bretylium.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Bretylium.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Bretylium.Approved
UdenafilUdenafil may increase the antihypertensive activities of Bretylium.Approved, Investigational
UnoprostoneBretylium may increase the hypotensive activities of Unoprostone.Approved
UrapidilUrapidil may increase the hypotensive activities of Bretylium.Investigational
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Bretylium.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Bretylium.Approved
VerapamilBretylium may increase the bradycardic activities of Verapamil.Approved
VincamineBretylium may increase the hypotensive activities of Vincamine.Experimental
VinpocetineBretylium may increase the hypotensive activities of Vinpocetine.Investigational
XipamideBretylium may increase the hypotensive activities of Xipamide.Experimental
XylometazolineBretylium may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Bretylium.Approved, Vet Approved
ZofenoprilBretylium may increase the hypotensive activities of Zofenopril.Experimental
Food Interactions
Not Available

References

Synthesis Reference

Copp, F.C. and Stephenson, D.; US. Patent 3,038,004; June 5, 1962; assigned to Burroughs Wellcome & Co.

US3038004
General References
Not Available
External Links
Human Metabolome Database
HMDB15289
KEGG Drug
D00645
KEGG Compound
C06855
PubChem Compound
2431
PubChem Substance
46505320
ChemSpider
2337
ChEBI
3172
ChEMBL
CHEMBL1199080
Therapeutic Targets Database
DAP000939
PharmGKB
PA448662
RxList
RxList Drug Page
Wikipedia
Bretylium
ATC Codes
Not Available
AHFS Codes
  • 24:04.04.20
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntramuscular; Intravenous50 mg
SolutionIntravenous
SolutionIntramuscular; Intravenous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)238Fryer, R.I., Schmidt, R.A. and Sternbach, L.H.; U.S. Patent 3,100,770; August 13, 1963; assigned to Hoffmann-LaRoche Inc. Fryer, R.I., Schmidt, R.A. and Sternbach, L.H.; U.S. Patent 3,182,065; May 4, 1965; assigned to Hoffmann-LaRoche Inc. Fryer, R.I., Schmidt, R.A. and Sternbach, L.H.; US. Patent 3,182,067; May 4, 1965; assigned to Hoffmann-LaRoche Inc.
water solubilityFreely solubleNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000154 mg/mLALOGPS
logP-1.4ALOGPS
logP-1.1ChemAxon
logS-6.3ALOGPS
pKa (Strongest Acidic)17.58ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.89 m3·mol-1ChemAxon
Polarizability23.24 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier+0.9484
Caco-2 permeable+0.6831
P-glycoprotein substrateSubstrate0.5105
P-glycoprotein inhibitor INon-inhibitor0.9789
P-glycoprotein inhibitor IINon-inhibitor0.8742
Renal organic cation transporterNon-inhibitor0.6279
CYP450 2C9 substrateNon-substrate0.861
CYP450 2D6 substrateNon-substrate0.6999
CYP450 3A4 substrateSubstrate0.5132
CYP450 1A2 substrateNon-inhibitor0.6973
CYP450 2C9 inhibitorNon-inhibitor0.8505
CYP450 2D6 inhibitorNon-inhibitor0.8475
CYP450 2C19 inhibitorNon-inhibitor0.8038
CYP450 3A4 inhibitorNon-inhibitor0.9752
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6854
Ames testNon AMES toxic0.9045
CarcinogenicityCarcinogens 0.5905
BiodegradationNot ready biodegradable0.9157
Rat acute toxicity2.6214 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9291
hERG inhibition (predictor II)Inhibitor0.6322
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylmethylamines
Direct Parent
Phenylmethylamines
Alternative Parents
Benzylamines / Bromobenzenes / Aralkylamines / Aryl bromides / Tetraalkylammonium salts / Organopnictogen compounds / Organobromides / Organic salts / Hydrocarbon derivatives / Organic cations
Substituents
Benzylamine / Phenylmethylamine / Aralkylamine / Bromobenzene / Halobenzene / Aryl bromide / Aryl halide / Tetraalkylammonium salt / Quaternary ammonium salt / Amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
quaternary ammonium ion (CHEBI:3172)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Steroid hormone binding
Specific Function
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 th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
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:1334399]
  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:15121098]
  3. Dzimiri N, Almotrefi AA: Interaction of bretylium tosylate with guinea-pig myocardial Na(+)-K(+)-ATPase. Gen Pharmacol. 1991;22(5):935-8. [PubMed:1662173]
  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:1667290]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:54