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).
Norepinephrine–dopamine reuptake inhibitors are used for clinical depression , attention deficit hyperactivity disorder (ADHD), narcolepsy , and as antiparkinson agents.
List of NDRIs [ edit ]
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
Oxolinic acid
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 [ edit ]
The US 2011263651 compound
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
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 ]
^ 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, S. M. (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.
Adamantanes
Adenosine antagonists
Alkylamines
Ampakines
Arylcyclohexylamines
Benzazepines
Cholinergics
Convulsants
Eugeroics
Oxazolines
Phenethylamines
1-(4-Methylphenyl)-2-aminobutane
1-Phenyl-2-(piperidin-1-yl)pentan-3-one
1-Methylamino-1-(3,4-methylenedioxyphenyl)propane
2-Fuoroamphetamine
2-Fuoromethamphetamine
2-OH-PEA
2-Phenyl-3-aminobutane
2-Phenyl-3-methylaminobutane
2,3-MDA
3-Fuoroamphetamine
3-Fluoroethamphetamine
3-Fluoromethcathinone
3-Methoxyamphetamine
3-Methylamphetamine
3,4-DMMC
4-BMC
4-CMC
4-Ethylamphetamine
4-Fluoroamphetamine
4-Fluoromethamphetamine
4-MA
4-Methylbuphedrone
4-Methylcathinone
4-MMA
4-Methylpentedrone
4-MTA
6-FNE
AL-1095
Alfetamine
a-Ethylphenethylamine
Amfecloral
Amfepentorex
Amfepramone
Amidephrine
2-Amino-1,2-dihydronaphthalene
2-Aminoindane
5-(2-Aminopropyl)indole
2-Aminotetralin
Acridorex
Amphetamine (Dextroamphetamine , Levoamphetamine )
Amphetaminil
Arbutamine
β-Methylphenethylamine
β-Phenylmethamphetamine
Benfluorex
Benzedrone
Benzphetamine
BDB
BOH
3-Benzhydrylmorpholine
BPAP
Buphedrone
Bupropion
Butylone
Camfetamine
Cathine
Cathinone
Chlorphentermine
Cilobamine
Cinnamedrine
Clenbuterol
Clobenzorex
Cloforex
Clortermine
Cypenamine
D -Deprenyl
Denopamine
Dimethoxyamphetamine
Dimethylamphetamine
Dimethylcathinone
Dobutamine
DOPA (Dextrodopa , Levodopa )
Dopamine
Dopexamine
Droxidopa
EBDB
Ephedrine
Epinephrine
Epinine
Etafedrine
Ethcathinone
Ethylnorepinephrine
Ethylone
Etilamfetamine
Etilefrine
Famprofazone
Fencamfamin
Fencamine
Fenethylline
Fenfluramine (Dexfenfluramine , Levofenfluramine )
Fenproporex
Feprosidnine
Flephedrone
Fludorex
Formetorex
Furfenorex
Gepefrine
Hexapradol
Hexedrone
HMMA
Hordenine
4-Hydroxyamphetamine
5-Iodo-2-aminoindane
Ibopamine
IMP
Indanylamphetamine
Iofetamine
Isoetarine
Isoethcathinone
Isoprenaline
L -Deprenyl (Selegiline)
Lefetamine
Lisdexamfetamine
Lophophine
MBDB
MDA
MDBU
MDEA
MDMA
MDMPEA
MDOH
MDPR
MDPEA
Mefenorex
Mephedrone
Mephentermine
Metanephrine
Metaraminol
Mesocarb
Methamphetamine (Dextromethamphetamine , Levomethamphetamine )
Methoxamine
Methoxyphenamine
MMA
Methcathinone
Methedrone
Methoxyphenamine
Methylenedioxycathinone
Methylone
Mexedrone
MMDA
MMDMA
MMMA
Morforex
N,alpha-Diethylphenylethylamine
N-Benzyl-1-phenethylamine
N-Ethylbuphedrone
N-Ethylhexedrone
N,N-Dimethylphenethylamine
Naphthylamphetamine
Nisoxetine
Norepinephrine
Norfenefrine
Norfenfluramine
Normetanephrine
L -Norpseudoephedrine
Octopamine (drug)
Orciprenaline
Ortetamine
Oxifentorex
Oxilofrine
PBA
PCA
PCMA
PHA
Pentorex
Pentedrone
Pentylone
Phenatine
Phenpromethamine
Phentermine
Phenylalanine
Phenylephrine
Phenylpropanolamine
Pholedrine
PIA
PMA
PMEA
PMMA
PPAP
Phthalimidopropiophenone
Prenylamine
Propylamphetamine
Pseudoephedrine
Ropinirole
Salbutamol (Levosalbutamol )
Sibutramine
Synephrine
Theodrenaline
Tiflorex
Tranylcypromine
Tyramine
Tyrosine
Xylopropamine
Zylofuramine
Phenylmorpholines
Piperazines
Piperidines
Pyrrolidines
Racetams
Tropanes
Tryptamines
Others
Reuptake
inhibitors
DAT
(DRIs )
NET
(NRIs )
Others: Antihistamines (e.g., brompheniramine , chlorphenamine , pheniramine , tripelennamine )
Arylcyclohexylamines (e.g., ketamine , phencyclidine )
CP-39,332
Dopexamine
EXP-561
Fezolamine
Ginkgo biloba
Indeloxazine
Loxapine
Nefazodone
Nefopam
Opioids (e.g., methadone , pethidine (meperidine) , tapentadol , tramadol , levorphanol )
Pridefine
Tedatioxetine
Teniloxazine
Tofenacin
Tropanes (e.g., cocaine )
Ziprasidone
SERT
(SRIs )
Others: A-80426
Amoxapine
Antihistamines (e.g., brompheniramine , chlorphenamine , dimenhydrinate , diphenhydramine , mepyramine (pyrilamine) , pheniramine , tripelennamine )
Arylcyclohexylamines (e.g., esketamine , ketamine , phencyclidine )
CP-39332
Cyclobenzaprine
Dextromethorphan
Dextrorphan
Efavirenz
Etoperidone
EXP-561
Fezolamine
Litoxetine
LY-393558
Loxapine
Lubazodone
Medifoxamine
Mesembrine
Mifepristone
MIN-117 (WF-516)
N-Me-5-HT
Opioids (e.g., dextropropoxyphene , methadone , pethidine (meperidine) , levorphanol )
PIM-35
Pridefine
Roxindole
SB-649915
TGBA01AD
Tofenacin
Trazodone
Tropanes (e.g., cocaine )
Vortioxetine
Ziprasidone
VMATs
Releasing
agents
Others