Bretylium (also bretylium tosylate) is an antiarrhythmic agent. It blocks the release of noradrenaline from nerve terminals. In effect, it decreases output from the peripheral

sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...

. 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 Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

followed by low blood pressure and ventricular ectopy. Originally introduced in 1959 for the treatment of hypertension. Its use as an antiarrhythmic for ventricular fibrillation was discovered and patented by Marvin Bacaner in 1969 at the University of Minnesota. The

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...

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. On June 8, 2011 bretylium tosylate was announced as unavailable in the US after request of

Hospira Inc. Hospira was an American global pharmaceutical and medical device company with headquarters in Lake Forest, Illinois. It had approximately 19,000 employees. Before its acquisition by Pfizer, Hospira was the world's largest producer of generic in ...

to withdraw its

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from the market. Bretylium will remain on the

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's discontinued drug list since its withdrawal was not the result of a safety or effectiveness concern. In mid 2019, it was reintroduced.

Uses

The drug was used in

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

digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...

toxicity. Bretylium should be used only in an

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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. Its specificity for sympathetic nerves is achieved because it is a substrate for the noradrenaline transporter; hence, it accumulates inside nerve terminals which have this transporter.

Synthesis

Quaternization of ''o''-bromo-''N'',''N''-dimethylbenzylamine with ethyl-''p''-toluenesulfonate yields bretylium ''p''-toluenesulfonate (tosylate).

References

{{Ion channel modulators Adrenergic release inhibitors Antiarrhythmic agents Organobromides Potassium channel blockers Quaternary ammonium compounds