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Norepinephrine–dopamine reuptake inhibitor

Norepinephrine–dopamine reuptake inhibitor

The skeletal structure of dopamine

The skeletal structure of dopamine

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]

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

Uses

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

List of NDRIs

The skeletal structure of methylphenidate

The skeletal structure of methylphenidate

Many NDRIs exist, including the following:

  • Amineptine (Survector, Maneon, Directim)

  • Bupropion (Wellbutrin)[2]

  • Desoxypipradrol (2-DPMP)

  • Dexmethylphenidate (Focalin)

  • Difemetorex (Cleofil)

  • Diphenylprolinol (D2PM)

  • Ethylphenidate

  • Fencamfamine (Glucoenergan, Reactivan)

  • Fencamine (Altimina, Sicoclor)

  • Lefetamine (Santenol)

  • Methylenedioxypyrovalerone (MDPV)

  • Methylphenidate (Ritalin, Concerta, Metadate, Methylin, Rubifen, Stimdate)

  • Nomifensine (Merital)

  • O-2172

  • Phenylpiracetam (Phenotropil, Carphedon)

  • Pipradrol (Meretran)

  • Prolintane (Promotil, Katovit)

  • Pyrovalerone (Centroton, Thymergix)

  • Tametraline (CP-24,411)

  • WY-46824

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.

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 NDRIs, but analogous to trace amines.

Research compounds

The CA 2711977 compound

The CA 2711977 compound

The US 2011263651 compound

The US 2011263651 compound

CA 2711977 [[CITE|3|https://worldwide.espacenet.com/textdoc?DB=EPODOC&IDX=CA2711977]]
Compound5-HT-uptake IC50(μM)DA-uptake IC50(μM)NA-uptake IC50(μM)
Piperidine-4-carboxylic (3,4-dichloro-phenyl)-ethyl-amide0.370.0210.0097
Piperidine-4-carboxylic (3-bromo-4-chloro-phenyl)-ethyl-amide0.140.00780.005
Piperidine-4-carboxylic (3-4-dibromo-phenyl)-ethyl-amide0.120.00400.0031
US 2011263651 [[CITE|4|https://worldwide.espacenet.com/textdoc?DB=EPODOC&IDX=US2011263651]]
Compound5-HT-uptake IC50(μM)DA-uptake IC50(μM)NA-uptake IC50(μM)
N-(3,4-Dichloro-phenyl)-N-ethyl-4-piperidin-4-yl-butyramide0.570.0120.030
N-(3,4-Dichloro-phenyl)-N-ethyl-4-(1-methyl-piperidin-4-yl)-butyramide0.800.00690.012

See also

  • Monoamine reuptake inhibitor

  • Dopamine reuptake inhibitor

  • Norepinephrine reuptake inhibitor

References

[1]
Citation Linkbooks.google.comStephen M. Stahl (2 March 2009). Antidepressants. Cambridge University Press. p. 73. ISBN 978-0-521-75852-9. Retrieved 10 May 2012.
Sep 21, 2019, 2:25 AM
[2]
Citation Linkportal.issn.orgStahl, SM; Pradko, JF; Haight, BR; Modell, JG; Rockett, CB; Learned-Coughlin, S (2004). "A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor". Primary Care Companion to the Journal of Clinical Psychiatry. 6 (4): 159–166. doi:10.4088/PCC.v06n0403. ISSN 1523-5998. PMC 514842. PMID 15361919.
Sep 21, 2019, 2:25 AM
[3]
Citation Linkworldwide.espacenet.comCA 2711977
Sep 21, 2019, 2:25 AM
[4]
Citation Linkworldwide.espacenet.comUS 2011263651
Sep 21, 2019, 2:25 AM
[5]
Citation Linkbooks.google.comAntidepressants
Sep 21, 2019, 2:25 AM
[6]
Citation Linkwww.ncbi.nlm.nih.gov"A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor"
Sep 21, 2019, 2:25 AM
[7]
Citation Linkdoi.org10.4088/PCC.v06n0403
Sep 21, 2019, 2:25 AM
[8]
Citation Linkwww.worldcat.org1523-5998
Sep 21, 2019, 2:25 AM
[9]
Citation Linkwww.ncbi.nlm.nih.gov514842
Sep 21, 2019, 2:25 AM
[10]
Citation Linkwww.ncbi.nlm.nih.gov15361919
Sep 21, 2019, 2:25 AM
[11]
Citation Linken.wikipedia.orgThe original version of this page is from Wikipedia, you can edit the page right here on Everipedia.Text is available under the Creative Commons Attribution-ShareAlike License.Additional terms may apply.See everipedia.org/everipedia-termsfor further details.Images/media credited individually (click the icon for details).
Sep 21, 2019, 2:25 AM