Dopamine Reuptake Inhibitor

A dopamine reuptake inhibitor (DRI, DARI) is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the post-synaptic neuron is blocked from re-entering the pre-synaptic neuron. This in turn leads to increased extracellular concentrations of dopamine and therefore an increase in dopaminergic neurotransmission.

DRIs are frequently used in the treatment of conditions like ADHD and narcolepsy on account of their psychostimulant effects and in the treatment of obesity due to their appetite suppressant properties. They have also been used as antidepressants in the treatment of mood disorders, but their use for this indication has been limited on account of their abuse potential and restricted nature. Lack of Dopamine uptake and the increase in extracellular levels of dopamine have been linked to increased susceptibility to addictive behavior due to the increase in dopaminergic neurotransmission. The dopaminergic pathways are considered to be strong reward centers. Additionally, many DRIs such as cocaine are drugs of abuse due to the rewarding effects evoked by elevated synaptic concentrations of dopamine in the brain.

Due to their strong rewarding and reinforcing properties, DRIs are notorious for their high abuse potential and liability to cause cravings, addiction, and dependence. DRIs such as cocaine and methylphenidate and combination releasing agents such as amphetamine, methamphetamine, and MDMA ("ecstasy") are widely used recreationally throughout the world. It is estimated that there are approximately six million people addicted to cocaine in the United States alone.