Class of drug
Norepinephrine reuptake inhibitor Synonyms adrenergic reuptake inhibitor MeSH D018759 In Wikidata
A norepinephrine reuptake inhibitor (NRI , NERI ) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI ), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore can increase adrenergic neurotransmission .
Medical use [ ]
NRIs are commonly used in the treatment of conditions like ADHD and narcolepsy due to their psychostimulant effects and in obesity due to their appetite suppressant effects. They are also frequently used as antidepressants for the treatment of major depressive disorder , anxiety and panic disorder . Additionally, many addictive substances such as cocaine and methylphenidate possess NRI activity, though NRIs without combined dopamine reuptake inhibitor (DRI) properties are not significantly rewarding and hence are considered to have negligible potential for addiction.[1] [2] However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of NDRIs ) to produce rewarding effects in psychostimulant addictive substances.[3]
Depression [ ]
A meta analysis published in BMJ in 2011 concluded that the selective NRI reboxetine is indistinguishable from placebo in the treatment of depression.[4] A second review by the European Medicines Agency concluded that reboxetine was significantly more effective than placebo, and that its risk/benefit ratio was positive. The latter review, also examined the efficacy of reboxetine as a function of baseline depression, and concluded that it was effective in severe depression and panic disorder but did not show effects significantly superior to placebo in mild depression.[5]
A closely related type of drug is a norepinephrine releasing agent (NRA).
List of selective NRIs [ ]
Neurotransmitter transporters inhibitors
Noradrenaline (norepinephrine) transporter inhibitors
Many NRIs exist, including the following:
Selective norepinephrine reuptake inhibitors
Marketed
Atomoxetine (Strattera)
Reboxetine (Edronax, Vestra)
Viloxazine (Qelbree, Vivalan)
Never marketed
NRIs with activity at other sites
Marketed
Bupropion (Wellbutrin, Zyban)
Desipramine (Norpramin)
Nortriptyline (Pamelor)
Protriptyline (Vivactil)
Tapentadol (Nucynta)
Teniloxazine (Lucelan, Metatone)
Never marketed
Ciclazindol (Wy-23,409)
CP-39,332
Manifaxine (GW-320,659)
Radafaxine (GW-353,162)
Note: Only NRIs selective for the NET greater than the other two monoamine transporters (MATs) are listed here. For a list of NRIs that act at multiple MATs, see the other monoamine reuptake inhibitor pages such as NDRI , SNRI , and SNDRI .
See also [ ]
Monoamine reuptake inhibitor
Beta blocker , similar type of drugs used to block epinephrine and norepinephrine beta receptors
List of adrenergic drugs
References [ ]
^ Wee S, Woolverton WL (September 2004). "Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine". Drug and Alcohol Dependence . 75 (3): 271–6. doi :10.1016/j.drugalcdep.2004.03.010 . PMID 15283948 .
^ Gasior M, Bergman J, Kallman MJ, Paronis CA (April 2005). "Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys" . Neuropsychopharmacology . 30 (4): 758–64. doi :10.1038/sj.npp.1300593 . PMID 15526000 .
^ Rothman RB, Baumann MH, Dersch CM, et al. (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 .
^ Eyding D, Lelgemann M, Grouven U, et al. (2010). "Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials" . BMJ . 341 : c4737. doi :10.1136/bmj.c4737 . PMC 2954275 . PMID 20940209 .
^ "MHRA Public Assessment Report" (PDF) . Archived from the original (PDF) on 2014-04-27. Retrieved 2014-04-26 .
Stimulants
Adamantanes
Adapromine
Amantadine
Bromantane
Memantine
Rimantadine
Adenosine antagonists Alkylamines
Cyclopentamine
Cypenamine
Cyprodenate
Heptaminol
Isometheptene
Levopropylhexedrine
Methylhexaneamine
Octodrine
Propylhexedrine
Tuaminoheptane
Ampakines Arylcyclohexylamines Benzazepines
6-Br-APB
SKF-77434
SKF-81297
SKF-82958
Cathinones Cholinergics Convulsants Eugeroics Oxazolines Phenethylamines Phenylmorpholines Piperazines
2C-B-BZP
3C-PEP
BZP
CM156
DBL-583
GBR-12783
GBR-12935
GBR-13069
GBR-13098
GBR-13119
MeOPP
MBZP
oMPP
Vanoxerine
Piperidines
1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine
2-Benzylpiperidine
2-Methyl-3-phenylpiperidine
3,4-Dichloromethylphenidate
4-Benzylpiperidine
4-Fluoromethylphenidate
4-Methylmethylphenidate
Desoxypipradrol
Difemetorex
Diphenylpyraline
Ethylnaphthidate
Ethylphenidate
Methylnaphthidate
Isopropylphenidate
JZ-IV-10
Methylphenidate (Dexmethylphenidate )
Nocaine
Phacetoperane
Pipradrol
Propylphenidate
SCH-5472
Pyrrolidines Racetams
Oxiracetam
Phenylpiracetam
Phenylpiracetam hydrazide
Tropanes Tryptamines Others ATC code : N06B
Antiobesity agents /Anorectics (A08 )
Central
Stimulants
4-Methylamphetamine ‡
Amfecloral
Amfepentorex
Amfepramone
Aminorex ‡
Amphetamine
Amphetaminil
Atomoxetine
Benfluorex ‡
Benzphetamine
Bupropion (+naltrexone ; +zonisamide† )
Cathine
Cathinone
Chlorphentermine
Ciclazindol
Clobenzorex
Cloforex
Clominorex
Clortermine
Dexfenfluramine ‡
Dextroamphetamine
Dexmethylphenidate
Difemetorex ‡
Dimethylcathinone
Ephedrine
Ephedra ‡
Etilamfetamine
Etolorex
Fenbutrazate
Fencamfamin
Fenethylline
Fenfluramine (+phentermine ‡ )
Fenproporex
Fludorex
Fluminorex
Furfenorex ‡
Indanorex
Khat
Levopropylhexedrine
Lisdexamfetamine
Manifaxine
Mazindol
Mefenorex
Methamphetamine
Methylphenidate
Norfenfluramine
Pemoline
Pentorex
Phendimetrazine
Phenethylamine
Phenmetrazine
Phentermine (+topiramate )
Phenylpropanolamine
Picilorex
Pipradrol
Prolintane
Propylhexedrine
Pseudoephedrine
Pyrovalerone
Radafaxine
Reboxetine
Setazindol
Sibutramine ‡
Synephrine
Tesofensine
Viloxazine
Xylopropamine
Zylofuramine
Cannabinoid receptor antagonists Others
5-HTP
Beloranib §
Galactomannan
Glucomannan
L-DOPA
L-Phenylalanine
L-Tryptophan
L-Tyrosine
Lorcaserin
Lu AA-33810
Metformin
Naltrexone
Naloxone
Oxyntomodulin
P57
Peptide YY
Setmelanotide
Topiramate
Velneperit §
Yohimbine (Yohimbe )
Zonisamide
Water
Peripheral
# WHO-EM
‡ Withdrawn from market
Clinical trials :
† Phase III
§ Never to phase III
CNS stimulants
Amphetamine (Mixed amphetamine salts , Levoamphetamine , Dextroamphetamine , Lisdexamfetamine )
Methamphetamine
Methylphenidate
Dexmethylphenidate
Serdexmethylphenidate (+dexmethylphenidate )
Non-classicalCNS stimulants
Armodafinil
Atomoxetine
Modafinil
Viloxazine
α2 -adrenoceptor agonists Antidepressants
Amitriptyline
Bupropion
Buspirone
Desipramine
Duloxetine
Imipramine
Milnacipran
Moclobemide
Nortriptyline
Reboxetine
Venlafaxine
Miscellaneous/others Related articles
Attention deficit hyperactivity disorder (ADHD)
Attention deficit hyperactivity disorder management
Monoamine releasing agent
Dopamine (DA)
Dopamine transporter (DAT)
Dopamine reuptake inhibitor (DRI)
Norepinephrine (NE)
Norepinephrine transporter (NET)
Norepinephrine reuptake inhibitor (NRI)
Serotonin (5-HT)
Serotonin transporter (SERT)
Selective serotonin reuptake inhibitor (SSRI)
Serotonin-norepinephrine reuptake inhibitor (SNRI)
Norepinephrine-dopamine reuptake inhibitor (NDRI)
Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)
Antidepressants (N06A )
SSRIs
Citalopram
Escitalopram
Fluoxetine #
Fluvoxamine
Indalpine ‡
Paroxetine
Sertraline
Zimelidine ‡
SNRIs
Desvenlafaxine
Duloxetine
Levomilnacipran
Milnacipran
Tofenacin
Venlafaxine
NRIs
Atomoxetine
Reboxetine
Viloxazine
NDRIs
Amineptine ‡
Bupropion
Nomifensine ‡
NaSSAs SARIs
Etoperidone
Nefazodone
Trazodone
SMS Others
Agomelatine
Amisulpride
Esketamine
Etryptamine ‡
Indeloxazine
flupentixol
Ketamine §
Medifoxamine ‡
Metryptamine ‡
Oxaflozane ‡
Pivagabine ‡
Tandospirone
Teniloxazine
Tianeptine
Tricyclic and tetracyclic antidepressants
TCAs
Amineptine ‡
Amitriptyline #
Amitriptylinoxide
Butriptyline ‡
Clomipramine #
Demexiptiline ‡
Desipramine
Dibenzepin
Dimetacrine ‡
Dosulepin
Doxepin
Imipramine
Imipraminoxide ‡
Iprindole ‡
Lofepramine
Melitracen
Metapramine ‡
Nitroxazepine
Nortriptyline
Noxiptiline
Opipramol
Pipofezine
Propizepine ‡
Protriptyline
Quinupramine ‡
Tianeptine
Trimipramine
TeCAs
Amoxapine
Maprotiline
Mianserin
Mirtazapine
Setiptiline
Others
Monoamine oxidase inhibitors
Non-selective MAOA -selectiveMAOB -selective
Adjunctive therapies
Atypical antipsychotics (aripiprazole , brexpiprazole , lurasidone , olanzapine , quetiapine , risperidone )
Buspirone
Lithium (lithium carbonate , lithium citrate )
Thyroid hormones (triiodothyronine (T3 ), levothyroxine (T4 ))
Miscellaneous
Ademetionine (SAMe )
Hypericum perforatum (St. John's Wort)
Oxitriptan (5-HTP )
Rubidium chloride (RbCl)
Tryptophan
# WHO-EM
‡ Withdrawn from market
Clinical trials :
† Phase III
§ Never to phase III
Monoamine reuptake inhibitors
DAT (DRIs )
Piperazines: DBL-583
GBR-12783
GBR-12935
GBR-13069
GBR-13098
Nefazodone
Vanoxerine
Piperidines: 4-Fluoropethidine
Benocyclidine (BTCP)
Desoxypipradrol
Dexmethylphenidate
Difemetorex
Ethylphenidate
HDMP-28
Methylphenidate
Pethidine (meperidine)
Phencyclidine
Pipradrol
Serdexmethylphenidate
Tenocyclidine
Pyrrolidines: Diphenylprolinol
MDPV
Naphyrone
Prolintane
Pyrovalerone
Tropanes: Altropane
Benzatropine (benztropine)
Brasofensine
CFT
Cocaine
Dichloropane
Difluoropine
Etybenzatropine (ethybenztropine)
FE-β-CPPIT
FP-β-CPPIT
Ioflupane (123 I)
RTI-55
RTI-112
RTI-113
RTI-121
RTI-126
RTI-150
RTI-177
RTI-229
RTI-336
Tesofensine
Troparil
Tropoxane
WF-11
WF-23
WF-31
WF-33
NET (NRIs )
Norepinephrine–dopamine reuptake inhibitors: Amineptine
Bupropion
Fencamine
Fencamfamin
Hydroxybupropion
Lefetamine
Levophacetoperane
LR-5182
Manifaxine
Methylphenidate
Nomifensine
O-2172
Radafaxine
Serdexmethylphenidate
Solriamfetol
Tricyclic antidepressants: Amitriptyline
Butriptyline
Cianopramine
Clomipramine
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Melitracen
Nortriptyline
Protriptyline
Trimipramine
Tetracyclic antidepressants: Amoxapine
Maprotiline
Mianserin
Oxaprotiline
Setiptiline
Others: Antihistamines (e.g., brompheniramine , chlorphenamine , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., ketamine , phencyclidine )
Dopexamine
Ephenidine
Ginkgo biloba
Indeloxazine
Nefazodone
Opioids (e.g., desmetramadol , methadone , pethidine (meperidine) , tapentadol , tramadol , levorphanol )
SERT (SRIs )
Selective serotonin reuptake inhibitors and serotonin receptor modulators: Etoperidone
Litoxetine
Lubazodone
LY-393558
Quipazine
SB-649915
TGBA01AD
Trazodone
Vilazodone
Vortioxetine
Serotonin–norepinephrine reuptake inhibitors: Atomoxetine (tomoxetine)
Bicifadine
Desvenlafaxine
Duloxetine
Eclanamine
Levomilnacipran
McN5652
Milnacipran
N-Methyl-PPPA
PPPA
Tofenacin
Venlafaxine
Tricyclic antidepressants: Amitriptyline
Cianopramine
Clomipramine
Cyanodothiepin
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Nortriptyline
Pipofezine
Protriptyline
Others:
Amoxapine
Antihistamines (e.g., brompheniramine , chlorphenamine , dimenhydrinate , diphenhydramine , mepyramine (pyrilamine) , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., 3-MeO-PCP , esketamine , ketamine , methoxetamine , phencyclidine )
Cyclobenzaprine
Delucemine
Dextromethorphan
Dextrorphan
Efavirenz
Hypidone
Medifoxamine
Mesembrine
Mifepristone
MIN-117 (WF-516)
N-Me-5-HT
Opioids (e.g., dextropropoxyphene , methadone , pethidine (meperidine) , levorphanol , tapentadol , tramadol )
Roxindole
VMATs
Amiodarone
Amphetamines (e.g., amphetamine , methamphetamine , MDMA )
Bietaserpine
Deserpidine
Deutetrabenazine
Dihydrotetrabenazine
Efavirenz
GBR-12935
Ibogaine
Ketanserin
Lobeline
Reserpine
Rose bengal
Tetrabenazine
Valbenazine
Vanoxerine (GBR-12909)
Others
DAT modulators: Agonist-like: SoRI-9804
; Antagonist-like: SoRI-20041
See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins