Chemical Properties
White Solid
Originator
Bretylate,Wellcome,UK,1973
Uses
Bretylium tosylate has a biphasic response, initially inducing norepinephrine release followed by sympathetic ganglionic blockade. Bretylium tosylate is a class III antiarrhythmic agent and a competitive inhibitor of acetylcholinesterase.
Definition
ChEBI: The tosylate salt of bretylium. It blocks noradrenaline release 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 fibril
ation.
Manufacturing Process
N-o-Bromobenzyl-N,N-dimethylamine (100g) and ethyl p-toluenesulfonate (94
g) were mixed and warmed to 50°-60°C; after standing for either (a) a
minimum of 96 hours at 15°-20°C or (b) a minimum of 18 hours at 50°-60°C
and cooling to room temperature, a hard, crystalline mass was formed.
Recrystallization of this product from acetone (2.0 ml/g of crude solid),
followed by filtration and drying to 60°C gave N-o-bromobenzyl-N-ethyl-N,Ndimethylammonium
p-toluenesulfonate as a white, crystalline solid, MP 97°-
99°C. For this procedure it was necessary that the reactants were
substantially colorless and of a high purity.
brand name
Bretylol (Mayne).
Therapeutic Function
Adrenergic blocker; Antiarrhythmic
General Description
Bretylium tosylate, (o-bromobenzyl)ethyl dimethylammonium p-toluenesulfonate(Bretylol), is an extremely bitter, white, crystalline powder.The chemical is freely soluble in water and alcohol.Bretylium tosylate is an adrenergic neuronal-blockingagent that accumulates selectively in the neurons anddisplaces norepinephrine. Because of this property,bretylium was used initially, under the trade name ofDarenthin, as an antihypertensive agent. It caused posturaldecrease in arterial pressure. This use was discontinuedbecause of the rapid development of tolerance, erratic oralabsorption of the quaternary ammonium compound, andpersistent pain in the parotid gland on prolonged therapy.
Clinical Use
Currently, bretylium is reserved for use in ventriculararrhythmias that are resistant to other therapy. Bretyliumdoes not suppress phase 4 depolarization, a common actionof other antiarrhythmic agents. It prolongs the effectiverefractory period relative to the action potential durationbut does not affect conduction time and is categorized asa class III antiarrhythmic agent. Because bretylium doesnot have properties similar to those of the other antiarrhythmicagents, it has been suggested that its action is aresult of its adrenergic neuronal-blocking properties; theantiarrhythmic properties of the drug, however, are notaffected by administration of reserpine. Bretylium is also alocal anesthetic, but it has not been possible to demonstratesuch an effect on atria of experimental animals, except atvery high concentrations. Therefore, the precise mechanismof the antiarrhythmic action of bretylium remains tobe resolved.
Side effects
The major adverse effect associated with bretylium tosylate is hypotension, including
orthostatic hypotension, which may be very severe.
