Bretylium is a class III antiarrhythmic agent and an inhibitor of the Na+/K+-ATPase (IC50 = 4.5 mM).1 Bretylium also has antiadrenergic activity, inhibiting auricular nerve stimulation-induced vasoconstriction in isolated rabbit ears and hypogastric nerve stimulation-induced contraction of isolated rabbit uterus.2 It inhibits neuroeffector calcium transients (NCTs), as well as increases action potential delay and the absolute refractory period, but does not inhibit field stimulus-induced CTs in isolated mouse vas deferens sympathetic nerve terminals.3 Bretylium prevents ventricular fibrillation in anesthetized dogs in a model of sudden coronary death when administered at a dose of 10 mg/kg.4 Formulations containing bretylium were previously used in the prevention and treatment of ventricular fibrillation.
1.Helms, J.B., Arnett, K.L., Gatto, C., et al.Bretylium, an organic quaternary amine, inhibits the Na,K-ATPase by binding to the extracellular K-siteBlood Cells Mol. Dis.32(3)394-400(2004) 2.Boura, A.L., Copp, F.C., and Green, A.F.New antiadrenergic compoundsNature184BA70-BA71(1959) 3.Brain, K.L., and Cunnane, T.C.Bretylium abolishes neurotransmitter release without necessarily abolishing the nerve terminal action potential in sympathetic terminalsBr. J. Pharmacol.153(4)831-839(2007) 4.Holland, K., Patterson, E., and Lucchesi, B.R.Prevention of ventricular fibrillation by bretylium in a conscious canine model of sudden coronary deathAm. Heart J.105(5)711-717(1983)