Vanoxerine

Vanoxerine (GBR-12909) is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor (DRI). GBR-12909 binds to the target site on the dopamine transporter (DAT) ~ 50 times more strongly than cocaine, but simultaneously inhibits the release of dopamine. This combined effect only slightly elevates dopamine levels, giving vanoxerine only mild stimulant effects. Vanoxerine has also been observed to be a potent blocker of the IKr (hERG) channel.

Vanoxerine as a treatment for cocaine dependence

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 was hoped that vanoxerine would 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.

GBR-13098

GBR-13098 is a psychostimulant and selective dopamine uptake inhibitor.

Blocking the endogenous striatal dopamine (DA) transporter with GBR-13098 in mice has been shown to prevent damage to the DA nerve terminals caused by malonate. It was suggested that DA transporter inhibitors like GBR-13098 could be used to prevent or treat neurodegenerative disorders caused by the effect of mitochondrial dysfunction on DA homeostasis.

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GBR-12935

GBR-12935 is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor. It was originally developed in its ³H radiolabelled form for the purpose of mapping the distribution of dopaminergic neurons in the brain by selective labelling of dopamine transporter proteins. This has led to potential clinical uses in the diagnosis of Parkinson's disease, although selective radioligands such as Ioflupane (¹²³I) are now available for this application. GBR-12935 is now widely used in animal research into Parkinson's disease and the dopamine pathways in the brain.

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