Drugs & Medication

Dopamine Reuptake Inhibitors (DARI), Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the reuptake of extracellular dopamine back into the presynaptic cell by blocking the cell membrane-spanning dopamine transporter. This usually results in an elevated extracellular dopamine level.

DARIs bind at the transporter molecule and form a non-covalent complex with it. As far as the DARI-molecule is large enough (which is normally the case), it suppresses the binding of other substances that are transporter substrates – as endogenous compounds (like dopamine) and drugs (e.g. amphetamine).

A very special kind of pseudo-DARIs have been developed by scientists. It is a smaller compound that binds covalently at the transporter, permanently blocks the binding of larger drugs like cocaine, but allows small molecules like dopamine to pass through.

A potent dopamine reuptake inhibitor is amineptine which is now banned in most countries including the USA. Other drugs which impact the level of dopamine in the brain include bupropion (Welbutrin, Zyban), venlafaxine (Efexor), duloxetine (Cymbalta), sertraline (Zoloft) (at high doses), MAOIs, cocaine, Benztropine, Nomifensine, Mazindol, amphetamines and a new class of reuptake inhibitors, the GBR series, such as GBR12909 (vanoxerine).

In general, the abuse potential of DAR inhibitors depends on how they affect the pattern of dopamine release and reuptake. Compounds that inhibit reuptake and also induce release of dopamine (such as methamphetamine or phenmetrazine), or compounds that inhibit reuptake but have no effect on release (such as cocaine or methylphenidate) tend to be addictive drugs with potential for abuse in humans. On the other hand, compounds that inhibit reuptake but also inhibit release of dopamine (such as mazindol, bupropion and vanoxerine) have mild stimulant effects and little abuse potential, and can be used to treat stimulant addiction.

Dopamine reuptake inhibitors

• Bupropion (Wellbutrin, Zyban)
• Amineptine (Maneon, Survector)
• Phenmetrazine (Preludin)
• Methylphenidate (Ritalin, Rubifen)
• Vanoxerine (GBR-12909)
• CFT (WIN-35428)
• Dextromethorphan (DXM)

See also

SSRI

Further reading

• Runyon SP, Carroll FI (2006): "Dopamine transporter ligands: recent developments and therapeutic potential", Curr.Top.Med.Chem. 6(17):1825-43. Abstract (Review)