en Norepinephrine%E2%80%93dopamine reuptake inhibitor

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a type of drug that inhibits the reuptake of the monoamine neurotransmitters norepinephrine and dopamine and thereby increases extracellular levels of these neurotransmitters and noradrenergic and dopaminergic neurotransmission.^[1] They work by competitively and/or noncompetitively inhibiting the norepinephrine transporter (NET) and dopamine transporter (DAT).^[1]

NDRIs are used clinically in the treatment of conditions including attention deficit hyperactivity disorder (ADHD), narcolepsy, and depression. Examples of well-known NDRIs include methylphenidate and bupropion.

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

List of NDRIs

Many NDRIs exist, including the following:

Some NDRIs, such as methylphenidate, may not act as simple NDRIs but rather as DAT "inverse agonists" (and possibly also analogously at the NET as well).^[3] If this theory is correct, then methylphenidate and other agents like cocaine may not be acting primarily as monoamine reuptake inhibitors but instead as robust monoamine releasing agent-esque drugs, albeit via a different mechanism of action that conventional substrate-type monoamine releasing agents.^[3]

Norepinephrine–dopamine releasing agents (NDRAs) like amphetamine and methamphetamine not only induce monoamine release but also act as monoamine reuptake inhibitors to a lesser extent and hence are additionally NDRIs.^[4]^[5]

^ ^a ^b Stephen M. Stahl (2 March 2009). Antidepressants. Cambridge University Press. p. 73. ISBN 978-0-521-75852-9. Retrieved 10 May 2012.
^ Stahl, 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.
^ ^a ^b Heal DJ, Gosden J, Smith SL (December 2014). "Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine". Neuropharmacology. 87: 19–40. doi:10.1016/j.neuropharm.2014.06.012. PMID 24953830.
^ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". Eur J Pharmacol. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135.
^ Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707.