Vanoxerine

Vanoxerine, also known as GBR-12909, is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor. GBR-12909 binds to the target site on the dopamine reuptake transporter around 500 times more strongly than cocaine, but has only mild stimulant effects, because as well as inhibiting the reuptake of dopamine, GBR-12909 inhibits dopamine release, and so produces only a slight elevation of dopamine levels.

Vanoxerine has been researched for use in treating cocaine dependence both as a substitute for cocaine and to block the rewarding effects. This strategy of using a competing agonist with a longer half-life has been successfully used to treat addiction to opiates such as heroin by substituting with methadone. It is hoped that vanoxerine will be of similar use in treating cocaine addiction.

Research also indicates that vanoxerine may have additional mechanisms of action including antagonist action at nicotinic acetylcholine receptors, and it has also been shown to reduce the consumption of alcohol in animal models of alcohol abuse.

Vanoxerine has been through human trials up to Phase 2, but has not been developed for clinical use, although it is still being researched.

A decanoate ester of vanoxerine, DBL-583, has also been developed, which slowly breaks down in the body and lasts for up to a month after a single injection.