Vanoxerine is an investigational drug that is a selective dopamine transporter antagonist that has not been approved for therapeutic use but is indicated to help treat cocaine addiction. It was developed as a treatment for depression but was found to have a higher affinity for the dopamine reuptake transporter with a slower dissociation rate than cocaine, indicating its use in cocaine addiction. Vanoxerine does have a moderate potential to be abused by humans as it stimulates the nervous system through the reuptake of norepinephrine and dopamine, which prolongs their duration in the synapse so that they can bind more readily to the receptors. This drug can inhibit cocaine binding sites at the dopamine transporters. The mechanism is not fully understood, but may be similar to other dopamine reuptake inhibitors where Vanoxerine would cross the blood-brain barrier through diffusion. Dopamine is synthesized in the ventral tegmental area of the brain from tyrosine being synthesized into L-dopa by the enzyme Tyrosine 3-monooxygenase . L-Dopa is then synthesized into dopamine with the enzyme aromatic-L-amino-acid decarboxylase. Dopamine then travels to the prefrontal cortex, which is released into the synapse when the neuron is stimulated and fires. Vanoxerine binds to the sodium-dependent dopamine transporter, preventing dopamine from re-entering the presynaptic neuron. The dopamine then binds to Dopamine D4 receptors on the postsynaptic membrane. The dopamine D4 receptor activates the Gi protein cascade which inhibits adenylate cyclase. This prevents adenylate cyclase from catalyzing ATP into cAMP.

Vanoxerine Dopamine Reuptake Inhibitor Pathway References