Norepinephrine-dopamine reuptake inhibitors

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.

A closely related type of drug is a norepinephrine-dopamine releasing agent (NDRA).

Norepinephrine–dopamine reuptake inhibitors are used for clinical depression, attention deficit hyperactivity disorder (ADHD), narcolepsy, and as antiparkinson agents.

Many NDRIs exist, including the following:

Amphetamine and many of its immediate derivatives (i.e., the substituted amphetamines) are also both non-competitive and competitive inhibitors of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT) proteins. Amphetamine itself has comparatively low affinity for SERT relative to DAT and NET. Consequently, amphetamine is usually classified as an NDRI instead of an SNDRI. However, the substituted amphetamines have a very diverse effects profile, and many of them have significant inhibiting effects on the SERT.