It was previously indicated as a treatment for Parkinson’s disease and depression; however, it had no significant benefit with these diseases. Medical uses Vanoxerine is a potentially effective treatment for abnormal heart rhythms. A significant cause of abnormal heart rhythms is reentry, an electrophysiologic event in which the proliferating signal refuses to terminate, and endures to preexcite the heart after the refractory period. It is likely that vanoxerine acts to prevent reentrant circuits. Vanoxerine terminates atrial flutters and atrial fibrillations (both cardiac abnormal heart rhythms) by blocking the recirculating electrical signal, and preventing the reformation of the reentrant circuit. Vanoxerine has also shown a tendency to reduce the recurrence of cardiac arrhythmias, as it was exceedingly difficult to reproduce an atrial flutter or fibrillation in a subject that had been taking vanoxerine. Experiments have successfully been performed on cell cultures, canine hosts and testing has moved towards human trials. In clinical human trials with increasing dosages, vanoxerine has shown to have a highly favourable therapeutic index, showing no side effects at concentrations much higher than the therapeutic dose. In canines, the effective therapeutic dose was between 76 ng/ml and 99 ng/ml, however the drug reached plasma concentrations of 550 ng/ml without harmful side effects, presenting a desirable therapeutic index. One of the major benefits of vanoxerine is that it does not appear to cause the same harmful side effects as its most comparable contender, amiodarone. Cellular mechanism At a cellular level, vanoxerine acts to block cardiac ion channels. Vanoxerine is a multichannel blocker, acting on IKr (potassium), L-type calcium and sodium ion channels. By blocking these specific channels, there is a prolongation of the action potential of the cell, preventing reactivation by a reentrant circuit. The block is strongly frequency dependant: as the pacing of the heart increases so does the frequency of ion channel blocking by vanoxerine. Molecular mechanism At this time, little is known about the molecular mechanism of vanoxerine, and steps are being made towards understanding how vanoxerine operates on a molecular level. References Dopamine reuptake inhibitors Nicotinic antagonists 1-(2-(Bis(4-fluorophenyl)methoxy)ethyl)piperazines VMAT inhibitors