A dopamine reuptake inhibitor (DRI) is a class of

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

which acts as a

reuptake inhibitor Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracel ...

of the

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

by blocking the action of the

dopamine transporter The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

is blocked from re-entering the

presynaptic In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

neuron. This results in increased

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

s of dopamine and increase in

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...

. DRIs are used in the treatment of

attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

(ADHD) and

narcolepsy Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...

for their

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

effects, and in the treatment of

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

and

binge eating disorder Binge eating disorder (BED) is an eating disorder characterized by frequent and recurrent binge eating episodes with associated negative psychological and social problems, but without the compensatory behaviors common to bulimia nervosa, OSFE ...

for their

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

effects. They are sometimes used as

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s in the treatment of

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the ''Diagnostic ...

s, but their use as antidepressants is limited given that strong DRIs have a high

abuse potential Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions ...

and legal restrictions on their use. Lack of dopamine reuptake and the increase in extracellular levels of dopamine have been linked to increased susceptibility to addictive behavior given increase in

. The

dopaminergic pathways Dopaminergic pathways (dopamine pathways, dopaminergic projections) in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine contro ...

are considered to be strong reward centers. Many DRIs such as

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

are drugs of abuse due to the rewarding effects evoked by elevated synaptic concentrations of

in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

Medical uses

The following drugs have DRI action and have been or are used clinically specifically for this property:

amineptine Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family. It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a le ...

dexmethylphenidate Dexmethylphenidate, sold under the brand name Focalin among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. ...

, difemetorex, fencamfamine,

lefetamine Lefetamine (Santenol) is a drug which is a stimulant and also an analgesic with effects comparable to codeine. Discovery The parent structure of lefetamine, 1,2-diphenylethylamine was first synthesized in the 1940s and showed weak analgesic ...

, levophacetoperane, medifoxamine,

mesocarb Mesocarb, sold under the brand name Sidnocarb or Sydnocarb and known by the developmental code name MLR-1017, is a psychostimulant medication which has been used in the treatment of psychiatric disorders and for a number of other indications in ...

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

nomifensine Nomifensine, formerly sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI) drug that was developed in the 1960s by Hoechst AG (now Sanofi-Aventis), who then test marketed it in the United States ...

pipradrol Pipradrol, also known by its brand name Meratran, is a mild central nervous system stimulant that acts as a norepinephrine-dopamine reuptake inhibitor. Developed in the United States in the 1940s and patented in 1953, pipradrol was initially m ...

, prolintane, and

pyrovalerone (Centroton, 4-Methyl-β-keto-prolintane, Thymergix, O-2371) is a central nervous system (CNS) stimulant that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was developed in the 1980s and had briefly been approved in Spain an ...

. The following drugs are or have been used clinically and possess only weak DRI action, which may or may not be clinically-relevant:

adrafinil Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly. It was also used off-label by individuals w ...

armodafinil Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It is also used off-label ...

bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...

, mazindol,

modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and wakefulness-promoting agent, eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characteri ...

nefazodone Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant medication which is used in the treatment of depression and for other uses. Nefazodone was withdrawn in most countries by ...

sertraline Sertraline, sold under the brand name Zoloft among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, socia ...

, and sibutramine. The following drugs are or have been clinically used but only coincidentally have DRI properties:

benzatropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is n ...

diphenylpyraline Diphenylpyraline (DPP; sold as Allergen, Arbid, Belfene, Diafen, Hispril, Histyn, Lergobine, Lyssipol, Mepiben, Neargal) is a first-generation antihistamine with anticholinergic effects of the benzhydryl, diphenylpiperidine class. It is marketed ...

etybenzatropine Etybenzatropine (INN), also known as ethybenztropine (USAN, BAN) and tropethydrylin, is a synthetic anticholinergic and antihistamine drug previously marketed under the trade names Panolid, Ponalid, and Ponalide for the treatment of Parkinson's ...

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

nefopam Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, with central stimulant and sympathomimetic properties that is primarily used to treat moderate to severe pain. History Nefopam i ...

pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Ot ...

(meperidine), and

tripelennamine Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less ...

. The following are a selection of some particularly notably abused DRIs:

MDPV Methylenedioxypyrovalerone (abbreviated MDPV, and also called monkey dust) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ing ...

naphyrone Naphyrone, also known as O-2482 and naphthylpyrovalerone, is a stimulant drug of the cathinone and naphthylaminopropane families. It was derived from pyrovalerone and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). ...

, and

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hall ...

(PCP).

Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

s, including

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

cathinone Cathinone (; also known as β-ketoamphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to t ...

, methcathinone,

mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug belonging to the amphetamine and cathinone classes. It is commonly referred to by slang names such as drone, , white magic, meow meow, and bubble. Chemically, it is similar to ...

, and

methylone Methylone, also known as 3,4-methylenedioxy-''N''-methylcathinone (MDMC), is an entactogen and stimulant drug of the amphetamine, cathinone, and benzodioxole families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). It is th ...

, are all DRIs as well, but are distinct in that they also behave, potentially more potently, as dopamine releasing agents (DRAs) (due to Yerkes–Dodson's law, 'more potently stimulated' may not equal more optimally functionally stimulated). There are very distinct differences in the mode of action between dopamine releasers/substrates & dopamine re-uptake inhibitors; the former are functionally

entropy Entropy is a scientific concept, most commonly associated with states of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the micros ...

-driven (i.e., relating to

hydrophobicity In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly intermolecular force, repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to b ...

) and the latter are

enthalpy Enthalpy () is the sum of a thermodynamic system's internal energy and the product of its pressure and volume. It is a state function in thermodynamics used in many measurements in chemical, biological, and physical systems at a constant extern ...

-driven (i.e., relating

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or othe ...

). Reuptake inhibitors such as cocaine induce hyperpolarization of cloned human DAT upon

oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...

s that are naturally found on neurons, whereas releasing agents induce de-polarization of the neuron membrane. The

wakefulness-promoting agent A wakefulness-promoting agent (WPA), or wake-promoting agent, is a drug that increases wakefulness and arousal. They are similar to but distinct from psychostimulants, which not only promote wakefulness but also produce other more overt central ...

and its analogues (e.g.,

) have been approved to treat

and

shift work sleep disorder Shift work sleep disorder (SWSD) is a circadian rhythm sleep disorder characterized by insomnia, excessive Somnolence, sleepiness, or both affecting people whose work hours overlap with the typical sleep period. Insomnia can be the difficulty to ...

. These act as weak (

micromolar Molar concentration (also called molarity, amount concentration or substance concentration) is the number of moles of solute per liter of solution. Specifically, It is a measure of the concentration of a chemical species, in particular, of a s ...

) DRIs, but this effect does not correlate with wakefulness-promoting effects, suggesting the effect is too weak to be of clinical significance. The conclusion is that these drugs promote wakefulness via some other mechanism. DRIs have been explored as potential antiaddictive agents in the context of replacement therapy strategies, analogous to nicotine replacement for treating tobacco addiction and

methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid used medically to treat chronic pain and opioid use disorder. Prescribed for daily use, the medicine relieves cravings and opioid withdrawal sym ...

replacement in the case of opioid addiction. DRIs have been explored as treatment for

addiction, and have shown to alleviate cravings and self-administration.

Monoamine reuptake inhibitor A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamin ...

s, including DRIs, have proven quite effective in managing excessive food consumption and regulating appetite in obese patients. Though such pharmacotherapy is still available, the majority of stimulant anorectics marketed for this purpose have been withdrawn or discontinued due to adverse side effects such as hypertension, valvulopathy, and drug dependence.

Pharmacology

DRIs may be divisible into two different types with different effects: (1) typical or conventional DRIs like

WIN-35428 WIN 35,428 (β-CFT, (–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane) is a stimulant drug used in scientific research. CFT is a phenyltropane based dopamine reuptake inhibitor and is structurally derived from cocaine. It is around 3-10x more ...

(β-CFT), and

that produce potent

euphoric Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...

, and reinforcing effects; and (2) atypical DRIs like

vanoxerine Vanoxerine is an investigational drug which is being evaluated for the treatment of heart arrhythmias and cocaine dependence. Vanoxerine is a piperazine derivative which has multiple pharmacological activities including acting as an dopamine re ...

(GBR-12909),

benztropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is ...

, and

, which do not produce such effects or have greatly reduced such effects. Moreover, atypical DRIs are often dysphoric at high doses. Typical DRIs may actually be acting as

dopamine releasing agent A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the Body (biology), body and/or brain. No binding selectivity, selective DRAs are currently known. However, non-selective DRAs, including norepinephrin ...

(DRA)-like agents that have been referred to as

(DAT) "

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

s" rather than as simple competitive reuptake inhibitors (which is what atypical DRIs are proposed to be). Typical DRIs are similar to

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

-type DRAs in their effects on brain dopamine levels and in their subjective and behavioral effects. In terms of maximal brain dopamine elevations, typical DRIs or DAT "inverse agonists" can increase levels by 500 to 1,500%, substrate-type DRAs by more than 1,000% (as high as 5,000% or more), and atypical DRIs or competitive reuptake inhibitors by less than or equal to 500%.

History

Until the 1950s, dopamine was thought to only contribute to the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

. It was not until dopamine was found in the brain in similar levels as norepinephrine that the possibility was considered that its biological role might be other than the synthesis of the

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

List of DRIs

Only DRIs which are selective for the DAT over the other

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

s (MATs) are listed below. For a list of DRIs that act at multiple MATs, see other

monoamine reuptake inhibitor A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamin ...

pages such as NDRI and SNDRI.

Selective dopamine reuptake inhibitors

Neurotransmitter transporters inhibitors

* α-Pyrrolidinoisohexanophenone ( α-PiHP) - very strong and very selective for the

, with little to no effect on the

and

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

transporters * 4-Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone * Altropane (O-587) * Amfonelic acid (WIN 25978) *

Amineptine Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family. It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a le ...

(has a reasonable degree of selectivity for dopamine over norepinephrine reuptake inhibition) *

BTCP Benocyclidine, also known as benzothiophenylcyclohexylpiperidine (BTCP), is a psychoactive recreational drug of the arylcyclohexylamine class which is related to phencyclidine (PCP). It was first described in a patent application naming Marc Car ...

(GK-13), same acronym as for breakthrough cancer pain. * 3C-PEP *

DBL-583 DBL-583 is a selective dopamine reuptake inhibitor of the piperazine chemical class. It is the decanoate ester of a hydroxy vanoxerine. DBL-583 breaks down very slowly in the body, lasting for up to a month after a single injection. See also ...

* Difluoropine (O-620) *

GBR-12783 GBR-12783 is a psychostimulant which acts as a selective dopamine reuptake inhibitor. See also * Vanoxerine * GBR-12935 * GBR-13069 * GBR-13098 * DBL-583 *LR-1111 LR-1111 is an analog of GBR-12935 that was discovered by Richard Rothman and ...

GBR-12935 GBR-12935 is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor. It was originally developed in its tritium, 3H isotopic labelling, radiolabelled form for the purpose of mapping the distribution of dopaminergic n ...

GBR-13069 GBR-13069 is a psychostimulant and selective dopamine reuptake inhibitor. See also * Vanoxerine * GBR-12783 * GBR-12935 * GBR-13098 * DBL-583 *LR-1111 LR-1111 is an analog of GBR-12935 that was discovered by Richard Rothman and co-workers in ...

GBR-13098 GBR-13098 is a psychostimulant and selective dopamine uptake inhibitor. Blocking the endogenous striatal dopamine (DA) transporter with GBR-13098 in mice has been shown to prevent damage to the DA nerve terminals caused by malonate. It was sugge ...

* GYKI-52895 *

Iometopane RTI(-''4229'')-55, also called RTI-55 or iometopane, is a phenyltropane-based psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991. RTI-55 is a non-selective dopamine reuptake inhibitor d ...

(β-CIT, RTI-55) *

Ethylphenidate Ethylphenidate (EPH) is a central nervous system (CNS) stimulant and a close analog of methylphenidate. Ethylphenidate acts as a norepinephrine–dopamine reuptake inhibitor, meaning it effectively boosts the levels of the norepinephrine and do ...

(more selective for DA vs NE reuptake inhibition compared to methylphenidate, but still has a marked effect on both) *

Modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and wakefulness-promoting agent, eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characteri ...

(relatively weak but very selective for the

, with little to no effect on the

transporters) *

Armodafinil Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It is also used off-label ...

(R-enantiomer of

; somewhat more potent at inhibiting DAT than racemic modafinil, with equally negligible action on NET and SERT) *

RTI-229 RTI-229, also known as (–)-3β-(4-iodophenyl)tropane-2β-pyrrolidine carboxamide and RTI-''4229''-229, is a potent and long-lasting stimulant drug which was developed in the 1990s as part of a large group of related analogues from the phenylt ...

Vanoxerine Vanoxerine is an investigational drug which is being evaluated for the treatment of heart arrhythmias and cocaine dependence. Vanoxerine is a piperazine derivative which has multiple pharmacological activities including acting as an dopamine re ...

(GBR-12909)

DRIs with substantial activity at other sites

Amantadine Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because ...

(also a weak

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to receptor antagonist, antagonize, or inhibit the action of, the NMDA, ''N''-Methyl-D-aspartate receptor (NMDA receptor, NMDAR). They are commonly used as anesthetics for humans and anima ...

) *

Benztropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is ...

(also muscarinic antagonist) *

Bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...

(also a more potent NRI and likely

NRA NRA may refer to: Organizations Asia and Oceania * National Railway Administration, the national railway regulator of China * National Recruitment Agency, Central Recruiting Agency of the Indian Government * New Revolutionary Alternative, an anar ...

due to bupropion's major metabolite

hydroxybupropion Hydroxybupropion (code name BW 306U), or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral ...

) *

Cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

* Fluorenol (extremely weak) * Medifoxamine (relatively weak) * Metaphit (irreversible; depletes dopamine) *

Methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

(has a mild degree of selectivity for dopamine over norepinephrine reuptake inhibition, although it significantly affects both) *

Dexmethylphenidate Dexmethylphenidate, sold under the brand name Focalin among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. ...

(the dextro

Diastereomer In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have di ...

(R,R steriomer) of methylphenidate. Is theorized to be more potent (twice as potent on a milli-to-milli basis) than racemic methylphenidate) *

Nomifensine Nomifensine, formerly sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI) drug that was developed in the 1960s by Hoechst AG (now Sanofi-Aventis), who then test marketed it in the United States ...

(Dual selective 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. *

Phenylpiracetam Phenylpiracetam, also known as fonturacetam () and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a psychostimulant, stimulant and nootropic medication used in Russia and certain other Eastern European countr ...

Isopropylphenidate Isopropylphenidate (also known as IPH and IPPD) is a piperidine based stimulant drug, closely related to methylphenidate, but with the methyl ester replaced by an isopropyl ester. It has similar effects to methylphenidate but with a longer durat ...

* Rimcazole *

Venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, pani ...

(weak) *

Solriamfetol Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of excessive sleepiness related to narcolepsy and sleep apnea. It is taken by mouth. Common side effects of solriamfetol include hea ...

(also norepinephrine reuptake inhibitor)

Other DRIs

* ''

Chaenomeles speciosa ''Chaenomeles speciosa'', the flowering quince, Chinese quince or Japanese quince,Bailey, L.H.; Bailey, E.Z.; the staff of the Liberty Hyde Bailey Hortorium. 1976. ''Hortus third: A concise dictionary of plants cultivated in the United States ...

'' (Flowering quince) *

Oroxylin A Oroxylin A is an O-methylated flavone, a chemical compound that can be found in the medicinal plants ''Scutellaria baicalensis'' and ''Scutellaria lateriflora'', and the '' Oroxylum indicum'' tree. It has demonstrated activity as a dopamine reup ...

(found in '' Oroxylum indicum'' and ''

Scutellaria baicalensis ''Scutellaria baicalensis'', with the common name Baikal skullcap or Chinese skullcap, is a species of flowering plant in the family Lamiaceae. Distribution The plant is native to China, Korea, Mongolia, and Russia in the Russian Far East and Si ...

'' (Skullcap))

References

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