Dopamine reuptake inhibitor

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. Dopamine is a powerful neurotransmitter that is responsible for reward and drive. It is the main chemical behind various feelings such as euphoria, orgasm, anger, addiction, love, pleasure and others. Dopamine reuptake inhibitors allow the dopamine to be absorbed for a longer period of time, and some drugs can create a drug induced euphoria. Cocaine, a DARI, is notorious for this effect. Also, prescription antidepressant drugs such as bupropion (Wellbutrin), and venlafaxine (Effexor) have this mechanism of action as well (of course, not as powerful). Nicotine also acts as a dopamine reuptake inhibitor, albeit a weaker one. Side effects from these drugs can be mixed. In some they induce euphoria, and in others they may induce restlessness and irritability; not unlike cocaine users.

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Mechanism

DARIs bind at the transporter molecule and form a non-covalent complex with it.^{[citation needed]} When the DARI-molecule is large enough, which is normally the case, it suppresses the binding of other substances that are transporter substrates, such as endogenous compounds (like dopamine) and drugs (e.g. amphetamine).^{[citation needed]}

Types

Amineptine is a potent dopamine reuptake inhibitor, and is now scheduled in most countries, including the USA. Other drugs which impact the level of dopamine in the brain include bupropion (Wellbutrin, Zyban), venlafaxine (Effexor), 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).

Abuse

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.^{[citation needed]}

On the other hand, compounds that inhibit reuptake but also inhibit release of dopamine, such as bupropion and vanoxerine, have mild stimulant effects and little abuse potential, and can be used to treat stimulant addiction.^{[citation needed]}

Some dopamine reuptake inhibitors

• Amineptine (Maneon, Survector)
• Bupropion (Wellbutrin, Zyban)
• Cocaine (an alkaloid)
• CFT (WIN-35428)
• Dextromethorphan (DXM)
• Methylenedioxypyrovalerone (MDPV)
• Methamphetamine (Desoxyn) ^[1]
• Methylphenidate (Ritalin, Rubifen, Concerta)
• Nicotine (an alkaloid)
• Phenmetrazine (Preludin)
• Troparil (CPT)
• Vanoxerine (GBR-12909)
• Venlafaxine (Effexor; at higher doses)

See also

• NERI
• SSRI
• NDRI
• SNRI
• SNDRI

Further reading

• Runyon SP, Carroll FI (2006). "Dopamine transporter ligands: recent developments and therapeutic potential". Current topics in medicinal chemistry 6 (17): 1825-43. PMID 17017960.

References

1. ^ Heal DJ, Frankland AT, Gosden J, et al (1992). "A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine". Psychopharmacology (Berl.) 107 (2-3): 303-9. PMID 1615130.