Norepinephrine-dopamine reuptake inhibitor

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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.[1] This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.[1]

Uses[edit]

Norepinephrine-dopamine reuptake inhibitors are used for clinical depression, ADD, ADHD, narcolepsy, and as antiparkinson agents.

List of NDRIs[edit]

Many NDRIs exist, including the following:

Amphetamine and many of its immediate derivatives (i.e., the substituted amphetamines) are also competitive inhibitors of the norepinephrine and dopamine transporter proteins. Amphetamine, itself also has very minor affinity for the serotonin transporter. But this action is rather insignificant, which is why amphetamine is usually classified as a NDRI. However, the substituted amphetamines have a very diverse effects profile, and many of them do, infact, have significant inhibiting effects on the SERT.

Amphetamine and many of the other substituted amphetamines are inhibitors of VMAT2 and potent agonists of the trace amine-associated receptor 1 (TAAR1); agonism of TAAR1 triggers phosphorylation events that result in both non-competitive reuptake inhibition and reversed transport direction of monoamine transporter proteins. As a result, monoamines flow out of the cell and into the synaptic cleft.

Thus, amphetamine and its derivatives have a pharmacological profile that is much different than classical NDRI's, but analogous to trace amines.

Note: Only NDRIs selective for the NET and DAT over the serotonin transporter (SERT) are listed here. For a list of NDRIs that also act at the SERT, see the SNDRI page.

Research Compounds[edit]

CA 2711977.svg
CA 2711977 
Compound 5-HT-uptake IC50(μM) DA-uptake IC50(μM) NA-uptake IC50(μM)
Piperidine-4-carboxylic (3,4-dichloro-phenyl)-ethyl-amide 0.37 0.021 0.0097
Piperidine-4-carboxylic (3-bromo-4-chloro-phenyl)-ethyl-amide 0.14 0.0078 0.005
Piperidine-4-carboxylic (3-4-dibromo-phenyl)-ethyl-amide 0.12 0.0040 0.0031
US2011263651.svg
US 2011263651 
Compound 5-HT-uptake IC50(μM) DA-uptake IC50(μM) NA-uptake IC50(μM)
N-(3,4-Dichloro-phenyl)-N-ethyl-4-piperidin-4-yl-butyramide 0.57 0.012 0.030
N-(3,4-Dichloro-phenyl)-N-ethyl-4-(1-methyl-piperidin-4-yl)-butyramide 0.80 0.0069 0.012

See also[edit]

References[edit]

  1. ^ a b Stephen M. Stahl (2 March 2009). Antidepressants. Cambridge University Press. p. 73. ISBN 978-0-521-75852-9. Retrieved 10 May 2012.