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Norepinephrine reuptake inhibitors (NRIs), also known as noradrenaline reuptake inhibitors (NARIs), are compounds that elevate the extracellular level of the neurotransmitter norepinephrine in the central nervous system by inhibiting its reuptake from the synaptic cleft into the presynaptic neuronal terminal. The drugs inhibit the class of neurotransmitter transporters known as norepinephrine transporters.
They have virtually no action at other monoamine transporters. However, this is not to say that NRIs exhibit nil effect on other monoamine levels per se; recent studies suggest a phenomenology of heteroreceptor regulation in the medial prefrontal cortex; whereby NRIs (for example Atomoxetine), speculatively via their indirect effect on the α1 and α2-adrenergic receptor, enhance dopamine release to synapse. However, unlike stimulant medications, this effect is exclusive to the PFC and absent in the striatum. Studies continue to investigate the precise neural mechanisms responsible.
List of NRIs
- Atomoxetine (Strattera)
- Reboxetine (Edronax)
- Viloxazine (Vivalan)
- Maprotiline (Ludiomil)
- Nortriptyline (Nortrilen)
- Bupropion (Wellbutrin) (since Bupropion additionally affects dopamine reuptake, it is also considered a member of the norepinephrine-dopamine reuptake inhibitor, or NDRI, class of drugs.)
- Radafaxine (A drug related to Bupropion presently in clinical trials)
Strattera is available in the United States and is indicated by the Food and Drug Administration (FDA) for the treatment of ADD and ADHD. Off-label uses include the treatment of depression and anxiety.
Reboxetine, unavailable in the United States and Canada, has been found to be effective at combating depression.
Radafaxine, a potent metabolite of Bupropion, is currently being developed by GlaxoSmithKline.
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