Bretylium

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Bretylium
Bretylium.svg
Systematic (IUPAC) name
N-(2-bromobenzyl)-N,N-dimethylethanaminium
Clinical data
MedlinePlus a682861
Pregnancy cat.
Legal status
Routes IV, IM
Pharmacokinetic data
Bioavailability NA
Protein binding NA
Metabolism None
Half-life 7-8 hours
Excretion Renal
Identifiers
CAS number 59-41-6 YesY
ATC code C01BD02
PubChem CID 2431
DrugBank DB01158
ChemSpider 2337 YesY
UNII RZR75EQ2KJ YesY
KEGG D00645 N
ChEBI CHEBI:3172 YesY
ChEMBL CHEMBL1199080 N
Chemical data
Formula C11H17BrN+
Mol. mass 243.163 g/mol
 N (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 hypertension followed by hypotension 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[edit]

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[edit]

It is used in physiological and pharmacological research as an inhibitor of sympathetic transmission. Its mechanism of action is the inhibition of neurotrasmitter 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[edit]

Bretylium synthesis:[10]

References[edit]