Bretylium

Bretylium

Systematic (IUPAC) name
N-(2-bromobenzyl)-N,N-dimethylethanaminium
Clinical data
MedlinePlus	a682861
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	US: ℞-only
Routes of administration	IV, IM
Pharmacokinetic data
Bioavailability	NA
Protein binding	NA
Metabolism	None
Biological half-life	7-8 hours
Excretion	Renal
Identifiers
CAS Number	59-41-6 Y
ATC code	C01BD02
PubChem	CID 2431
IUPHAR/BPS	7130
DrugBank	DB01158 Y
ChemSpider	2337 Y
UNII	RZR75EQ2KJ Y
KEGG	D00645 N
ChEBI	CHEBI:3172 Y
ChEMBL	CHEMBL1199080 N
Chemical data
Formula	C11H17BrN+
Molar mass	243.163 g/mol
SMILES Brc1ccccc1C[N+](CC)(C)C
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 Y Key:AAQOQKQBGPPFNS-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Bretylium (also bretylium tosylate) is an antiarrhythmic agent.^[1] It blocks the release of noradrenaline from nerve terminals. In effect, it decreases output from the peripheral sympathetic nervous system. It also acts by blocking K⁺ channels and is considered a class III antiarrhythmic. The dose is 5–10 mg/kg and side effects are high blood pressure followed by low blood pressure and ventricular ectopy.

Originally introduced in 1959 for the treatment of hypertension.^[2] Its use as an antiarrhythmic for ventricular fibrilation was discovered and patented by Marvin Bacaner in 1969 at the University of Minnesota.^[3]

The American Heart Association removed Bretylium from their 2000 ECC/ACC guidelines due to its unproven efficacy and ongoing supply problems. Many have cited these supply problems as an issue of raw materials needed in the production of Bretylium. By the release of the AHA 2005 ECC/ACC guidelines there is no mention of Bretylium and it is virtually unavailable throughout most of the world.^[4][5]

As of June 8, 2011 Bretylium Tosylate is permanently no longer available in the US after request of Hospira Inc. to withdraw its NDA from the market. Bretylium will remain on the FDA's discontinued drug list since its withdrawal was not the result of a safety or effectiveness concern.^[6]

Uses

It was used in emergency medicine, cardiology, and other specialties throughout the 1980s-1990s for the acute management of ventricular tachycardia and ventricular fibrillation refractory to other first line treatments such as defibrillation or lidocaine.^[7]

It is contraindicated in patients with AV (atrioventricular) heart block or digoxin toxicity.

Bretylium should be used only in an ICU or Emergency Department setting and should not be used elsewhere due to its dramatic actions and its predominant side effect of hypotension.

Experimental Uses

It is used in physiological and pharmacological research as an inhibitor of sympathetic transmission. Its mechanism of action is the inhibition of neurotransmitter release from sympathetic nerve terminals, both by the inhibition of action potentials in the nerve terminals and by other mechanisms.^[8] Its specificity for sympathetic nerves is achieved because it is a substrate for the noradrenaline transporter;^[9] hence, it accumulates inside nerve terminals which have this transporter.

Synthesis

Bretylium synthesis: Burroughs Wellcome Co. R. Tondeur, F. Binon, U.S. Patent 3,038,004 (1962).

Quaternization of o-bromo-N,N-dimethylbenzylamine with ethyl-p-toluenesulfonate yields bretylium sulfonate.

References