vanoxerine

Vanoxerine is a piperazine derivative and investigational small molecule drug developed primarily as a highly selective dopamine transporter antagonist. It was originally synthesized in the late 1970s for potential use as an antidepressant, but later evaluated for cocaine dependence, Parkinson's disease, depression, and most recently as an antiarrhythmic agent for atrial fibrillation and flutter. Mechanistically, vanoxerine potently inhibits dopamine reuptake by binding to the sodium-dependent dopamine transporter (DAT) with high affinity—approximately 50 times stronger than cocaine—while also inhibiting dopamine release. This results in only mild stimulant effects and blocks the rewarding effects of cocaine. In addition to its action on DAT, vanoxerine is a potent blocker of the cardiac hERG potassium channel (IKr), L-type calcium channels (Cav1.2), voltage-gated sodium channels (Nav1.5), and has nanomolar affinity for serotonin transporters; it may also act as an antagonist at nicotinic acetylcholine receptors and sigma receptors[1][2][3][5]. Clinical development included oral formulations and long-acting depot injections (Vanoxerine Consta) for cocaine dependence[6][7]. While phase IIb trials showed promise in arrhythmia conversion without significant proarrhythmic risk markers[8], phase III trials were terminated due to safety concerns related to cardiac events[2][5]. The drug has not been approved for any indication.

Brand names

Vanoxerine ConstaVANOREXINE CONSTA

Other names

VanoxerinaVanoxerinumVanoxerine [INN]