Norepinephrine–dopamine reuptake inhibitor
Drug that inhibits the reuptake of norepinephrine and dopamine
The skeletal structure of norepinephrine
The skeletal structure of dopamine
A norepinephrine–dopamine reuptake inhibitor (NDRI ) is a drug used for the treatment of clinical depression , attention deficit hyperactivity disorder (ADHD), narcolepsy , and the management of Parkinson's disease . The drug 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).
List of NDRIs
The skeletal structure of methylphenidate
Many NDRIs exist, including the following:
Amineptine (Survector, Maneon, Directim)
Bupropion (Wellbutrin, Zyban)[ 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)
Nomifensine (Merital)
O-2172
Phenylpiracetam (Phenotropil, Carphedon)
Pipradrol (Meretran)
Prolintane (Promotil, Katovit)
Pyrovalerone (Centroton, Thymergix)
Solriamfetol (Sunosi)
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 .
Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines.
Research compounds
The CA 2711977 compound
The US 2011263651 compound
See also
References
DAT Tooltip Dopamine transporter (DRIs Tooltip Dopamine reuptake inhibitors )
NET Tooltip Norepinephrine transporter (NRIs Tooltip Norepinephrine reuptake inhibitors )
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 Tooltip Serotonin transporter (SRIs Tooltip Serotonin reuptake inhibitors )
Others: A-80426
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 Tooltip Vesicular monoamine transporters Others