Dopamine transporter

Last updated

SLC6A3
Dopamine Transporter.jpg
Identifiers
Aliases SLC6A3 , solute carrier family 6 (neurotransmitter transporter), member 3, DAT, DAT1, PKDYS, solute carrier family 6 member 3, Dopamine transporter, PKDYS1
External IDs OMIM: 126455; MGI: 94862; HomoloGene: 55547; GeneCards: SLC6A3; OMA:SLC6A3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6531

13162

Ensembl

ENSG00000142319
ENSG00000276996

ENSMUSG00000021609

UniProt

Q01959

Q61327

RefSeq (mRNA)

NM_001044

NM_010020

RefSeq (protein)

NP_001035

NP_034150

Location (UCSC) Chr 5: 1.39 – 1.45 Mb Chr 13: 73.68 – 73.73 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 back into cytosol. In the cytosol, other transporters sequester the dopamine into vesicles for storage and later release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter. [5]

Contents

DAT is implicated in a number of dopamine-related disorders, including attention deficit hyperactivity disorder, bipolar disorder, clinical depression, eating disorders, and substance use disorders. The gene that encodes the DAT protein is located on chromosome 5, consists of 15 coding exons, and is roughly 64 kbp long. Evidence for the associations between DAT and dopamine related disorders has come from a type of genetic polymorphism, known as a variable number tandem repeat, in the SLC6A3 gene, which influences the amount of protein expressed. [6]

Function

DAT is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells, thus terminating the signal of the neurotransmitter. Dopamine underlies several aspects of cognition, including reward, and DAT facilitates regulation of that signal. [7]

Mechanism

DAT is a symporter that moves dopamine across the cell membrane by coupling the movement to the energetically-favorable movement of sodium ions moving from high to low concentration into the cell. DAT function requires the sequential binding and co-transport of two Na+ ions and one Cl− ion with the dopamine substrate. The driving force for DAT-mediated dopamine reuptake is the ion concentration gradient generated by the plasma membrane Na+/K+ ATPase. [8]

In the most widely accepted model for monoamine transporter function, sodium ions must bind to the extracellular domain of the transporter before dopamine can bind. Once dopamine binds, the protein undergoes a conformational change, which allows both sodium and dopamine to unbind on the intracellular side of the membrane. [9]

Studies using electrophysiology and radioactive-labeled dopamine have confirmed that the dopamine transporter is similar to other monoamine transporters in that one molecule of neurotransmitter can be transported across the membrane with one or two sodium ions. Chloride ions are also needed to prevent a buildup of positive charge. These studies have also shown that transport rate and direction is totally dependent on the sodium gradient. [10]

Because of the tight coupling of the membrane potential and the sodium gradient, activity-induced changes in membrane polarity can dramatically influence transport rates. In addition, the transporter may contribute to dopamine release when the neuron depolarizes. [10]

DAT–Cav coupling

Preliminary evidence suggests that the dopamine transporter couples to L-type voltage-gated calcium channels (particularly Cav1.2 and Cav1.3), which are expressed in virtually all dopamine neurons. [11] As a result of DAT–Cav coupling, DAT substrates that produce depolarizing currents through the transporter are able to open calcium channels that are coupled to the transporter, resulting in a calcium influx in dopamine neurons. [11] This calcium influx is believed to induce CAMKII-mediated phosphorylation of the dopamine transporter as a downstream effect; [11] since DAT phosphorylation by CAMKII results in dopamine efflux in vivo, activation of transporter-coupled calcium channels is a potential mechanism by which certain drugs (e.g., amphetamine) trigger neurotransmitter release. [11]

Protein structure

The initial determination of the membrane topology of DAT was based upon hydrophobic sequence analysis and sequence similarities with the GABA transporter. These methods predicted twelve transmembrane domains (TMD) with a large extracellular loop between the third and fourth TMDs. [12] Further characterization of this protein used proteases, which digest proteins into smaller fragments, and glycosylation, which occurs only on extracellular loops, and largely verified the initial predictions of membrane topology. [13] The exact structure of the Drosophila melanogaster dopamine transporter (dDAT) was elucidated in 2013 by X-ray crystallography. [14]

Location and distribution

Pharmacodynamics of amphetamine in a dopamine neuron
TAAR1 Dopamine.svg
via AADC
Interactive icon.svg
Amphetamine enters the presynaptic neuron across the neuronal membrane or through DAT. [15] Once inside, it binds to TAAR1 or enters synaptic vesicles through VMAT2. [15] [16] When amphetamine enters synaptic vesicles through VMAT2, it collapses the vesicular pH gradient, which in turn causes dopamine to be released into the cytosol (light tan-colored area) through VMAT2. [16] [17] When amphetamine binds to TAAR1, it reduces the firing rate of the dopamine neuron via G protein-coupled inwardly rectifying potassium channels (GIRKs) and activates protein kinase A (PKA) and protein kinase C (PKC), which subsequently phosphorylate DAT. [15] [18] [19] PKA phosphorylation causes DAT to withdraw into the presynaptic neuron (internalize) and cease transport. [15] PKC-phosphorylated DAT may either operate in reverse or, like PKA-phosphorylated DAT, internalize and cease transport. [15] Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a CAMKIIα-dependent pathway, in turn producing dopamine efflux. [20] [21]

Regional distribution of DAT has been found in areas of the brain with established dopaminergic circuitry, including the nigrostriatal, mesolimbic, and mesocortical pathways. [22] The nuclei that make up these pathways have distinct patterns of expression. Gene expression patterns in the adult mouse show high expression in the substantia nigra pars compacta. [23]

DAT in the mesocortical pathway, labeled with radioactive antibodies, was found to be enriched in dendrites and cell bodies of neurons in the substantia nigra pars compacta and ventral tegmental area. This pattern makes sense for a protein that regulates dopamine levels in the synapse.

Staining in the striatum and nucleus accumbens of the mesolimbic pathway was dense and heterogeneous. In the striatum, DAT is localized in the plasma membrane of axon terminals. Double immunocytochemistry demonstrated DAT colocalization with two other markers of nigrostriatal terminals, tyrosine hydroxylase and D2 dopamine receptors. The latter was thus demonstrated to be an autoreceptor on cells that release dopamine. TAAR1 is a presynaptic intracellular receptor that is also colocalized with DAT and which has the opposite effect of the D2 autoreceptor when activated; [15] [24] i.e., it internalizes dopamine transporters and induces efflux through reversed transporter function via PKA and PKC signaling.

Surprisingly, DAT was not identified within any synaptic active zones. These results suggest that striatal dopamine reuptake may occur outside of synaptic specializations once dopamine diffuses from the synaptic cleft.

In the substantia nigra, DAT is localized to axonal and dendritic (i.e., pre- and post-synaptic) plasma membranes. [25]

Within the perikarya of pars compacta neurons, DAT was localized primarily to rough and smooth endoplasmic reticulum, Golgi complex, and multivesicular bodies, identifying probable sites of synthesis, modification, transport, and degradation. [26]

Genetics and regulation

The gene for DAT, known as DAT1, is located on chromosome 5p15. [6] The protein encoding region of the gene is over 64 kb long and comprises 15 coding segments or exons. [27] This gene has a variable number tandem repeat (VNTR) at the 3’ end (rs28363170) and another in the intron 8 region. [28] Differences in the VNTR have been shown to affect the basal level of expression of the transporter; consequently, researchers have looked for associations with dopamine-related disorders. [29]

Nurr1, a nuclear receptor that regulates many dopamine-related genes, can bind the promoter region of this gene and induce expression. [30] This promoter may also be the target of the transcription factor Sp-1.

While transcription factors control which cells express DAT, functional regulation of this protein is largely accomplished by kinases. MAPK, [31] CAMKII, [20] [21] PKA, [15] and PKC [21] [32] can modulate the rate at which the transporter moves dopamine or cause the internalization of DAT. Co-localized TAAR1 is an important regulator of the dopamine transporter that, when activated, phosphorylates DAT through protein kinase A (PKA) and protein kinase C (PKC) signaling. [15] [33] Phosphorylation by either protein kinase can result in DAT internalization (non-competitive reuptake inhibition), but PKC-mediated phosphorylation alone induces reverse transporter function (dopamine efflux). [15] [34] Dopamine autoreceptors also regulate DAT by directly opposing the effect of TAAR1 activation. [15]

The human dopamine transporter (hDAT) contains a high affinity extracellular zinc binding site which, upon zinc binding, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux in vitro . [35] [36] [37] In contrast, the human serotonin transporter (hSERT) and human norepinephrine transporter (hNET) do not contain zinc binding sites. [37] Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of attention deficit hyperactivity disorder. [38]

Biological role and disorders

The rate at which DAT removes dopamine from the synapse can have a profound effect on the amount of dopamine in the cell. This is best evidenced by the severe cognitive deficits, motor abnormalities, and hyperactivity of mice with no dopamine transporters. [39] These characteristics have striking similarities to the symptoms of ADHD.

Differences in the functional VNTR have been identified as risk factors for bipolar disorder [40] and ADHD. [41] [42] Data has emerged that suggests there is also an association with stronger withdrawal symptoms from alcoholism, although this is a point of controversy. [43] [44] An allele of the DAT gene with normal protein levels is associated with non-smoking behavior and ease of quitting. [45] Additionally, male adolescents particularly those in high-risk families (ones marked by a disengaged mother and absence of maternal affection) who carry the 10-allele VNTR repeat show a statistically significant affinity for antisocial peers. [46] [47]

Increased activity of DAT is associated with several different disorders, including clinical depression. [48]

Mutations in DAT have been shown to cause dopamine transporter deficiency syndrome, an autosomal recessive movement disorder characterized by progressively worsening dystonia and parkinsonism. [49]

Pharmacology

The dopamine transporter is the target of substrates, dopamine releasers, transport inhibitors and allosteric modulators. [50] [51]

Cocaine blocks DAT by binding directly to the transporter and reducing the rate of transport. [12] In contrast, amphetamine enters the presynaptic neuron directly through the neuronal membrane or through DAT, competing for reuptake with dopamine. Once inside, it binds to TAAR1 or enters synaptic vesicles through VMAT2. When amphetamine binds to TAAR1, it reduces the firing rate of the postsynaptic neuron and triggers protein kinase A and protein kinase C signaling, resulting in DAT phosphorylation. Phosphorylated DAT then either operates in reverse or withdraws into the presynaptic neuron and ceases transport. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol. [15] [16] Amphetamine also produces dopamine efflux through a second TAAR1-independent mechanism involving CAMKIIα-mediated phosphorylation of the transporter, which putatively arises from the activation of DAT-coupled L-type calcium channels by amphetamine. [11]

The dopaminergic mechanisms of each drug are believed to underlie the pleasurable feelings elicited by these substances. [7]

Interactions

Dopamine transporter has been shown to interact with:

Apart from these innate protein-protein interactions, recent studies demonstrated that viral proteins such as HIV-1 Tat protein interacts with the DAT [57] [58] and this binding may alter the dopamine homeostasis in HIV positive individuals which is a contributing factor for the HIV-associated neurocognitive disorders. [59]

Ligands and modulators

Substrates

Dopamine reuptake inhibitors (DRIs)

Typical or classical cocaine-like blockers

These agents may actually act as dopamine releasing agent-esque DAT negative allosteric modulators or "inverse agonists". [76]

Atypical non-psychostimulant blockers

These agents may actually act as simple competitive DAT blockers without releaser-like "inverse agonist" activity. [76]

Unsorted blockers

Dopamine releasing agents (DRAs)

These agents are also known as substrate-type dopamine releasing agents and as DAT reversers. [76] [62]

Allosteric modulators

Positive allosteric modulators

Negative allosteric modulators

See also

Related Research Articles

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

<span class="mw-page-title-main">Dextroamphetamine</span> CNS stimulant and isomer of amphetamine

Dextroamphetamine is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. Dextroamphetamine is generally regarded as the prototypical stimulant.

<span class="mw-page-title-main">Adderall</span> Drug mixture used mainly to treat ADHD and narcolepsy

Adderall and Mydayis are trade names for a combination drug containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and levoamphetamine, the two enantiomers of amphetamine. Both enantiomers are stimulants, but differ enough to give Adderall an effects profile distinct from those of racemic amphetamine or dextroamphetamine, which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used illicitly as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles, which release the neurotransmitters into synapses, as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import.

Racetams, also sometimes known simply as pyrrolidones, are a class of drugs that share a pyrrolidone nucleus. Many, but not all, specifically have a 2-oxo-1-pyrrolidine acetamide (piracetam) nucleus. Some racetams, such as piracetam, aniracetam, oxiracetam, pramiracetam, and phenylpiracetam, are considered nootropics. Phenylpiracetam is also a stimulant. Others, such as levetiracetam, brivaracetam, and seletracetam, are anticonvulsants.

<span class="mw-page-title-main">Phenylpiracetam</span> Chemical compound

Phenylpiracetam, also known as fonturacetam and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, and attention, and memory problems, among other indications. It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities. The drug is taken by mouth.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Norepinephrine transporter</span> Protein-coding gene in the species Homo sapiens

The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene.

<span class="mw-page-title-main">Vesicular monoamine transporter 2</span> Mammalian protein found in Homo sapiens

The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the SLC18A2 gene. SLC18A2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, SLC18A2 function is also necessary for the vesicular release of the neurotransmitter GABA.

<span class="mw-page-title-main">Trace amine</span> Amine receptors in the mammalian brain

Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.

<span class="mw-page-title-main">Mesocarb</span> Stimulant drug

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 the Soviet Union and Russia. It is currently under development for the treatment of Parkinson's disease and sleep disorders. It is taken by mouth.

<span class="mw-page-title-main">Methamphetamine</span> Central nervous system stimulant

Methamphetamine is a potent central nervous system (CNS) stimulant that is mainly used as a recreational or performance-enhancing drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder (ADHD). It has also been researched as a potential treatment for traumatic brain injury. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. Methamphetamine properly refers to a specific chemical substance, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, but the hydrochloride salt, commonly called crystal meth, is widely used. Methamphetamine is rarely prescribed over concerns involving its potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy such as Adderall and Vyvanse. While pharmaceutical formulations of methamphetamine in the United States are labeled as methamphetamine hydrochloride, they contain dextromethamphetamine as the active ingredient. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine.

<span class="mw-page-title-main">TAAR1</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) that is primarily expressed in several peripheral organs and cells, astrocytes, and in the intracellular milieu within the presynaptic plasma membrane of monoamine neurons in the central nervous system (CNS). TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al. TAAR1 is one of six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS; it also affects immune system and neuroimmune system function through different mechanisms.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; monoamine releasing agents can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">Norepinephrine releasing agent</span> Catecholaminergic type of drug

A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into the synapse. This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine therefore an increase in adrenergic neurotransmission.

<span class="mw-page-title-main">Eugeroic</span> Drug for wakefulness and alertness

A eugeroic, or eugregoric, also known as a vigilance-promoting agent, is a type of drug that increases vigilance. The term has been used inconsistently and in multiple ways in the scientific literature, either to refer specifically to modafinil-type wakefulness-promoting agents or to refer to wakefulness-promoting agents generally. It was first introduced in the French literature in 1987 as a descriptor for modafinil-like wakefulness-promoting drugs and for purposes of distinguishing such drugs from psychostimulants. However, the term "eugeroic" has not been widely adopted in the literature, and instead the term "wakefulness-promoting agent" has been more widely used, both for modafinil-type drugs and other agents.

<span class="mw-page-title-main">Pseudophenmetrazine</span> Chemical compound

Pseudophenmetrazine is a psychostimulant compound of the morpholine class. It is the N-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine. In addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug. Relative to phenmetrazine, pseudophenmetrazine is of fairly low potency, acting as a modest releasing agent of norepinephrine (EC50 = 514 nM), while its (+)-enantiomer is a weak releaser of dopamine (EC50 = 1,457 nM) whereas its (−)-enantiomer is a weak reuptake inhibitor of dopamine (Ki = 2,691 nM); together as a racemic mixture with the two enantiomers combined, pseudophenmetrazine behaves overall more as a dopamine reuptake inhibitor (Ki = 2,630 nM), possibly due to the (+)-enantiomer blocking the uptake of the (−)-enantiomer into dopaminergic neurons and thus preventing it from inducing dopamine release. Neither enantiomer has any significant effect on serotonin reuptake or release (both Ki = >10,000 nM and EC50 = >10,000 nM, respectively).

<span class="mw-page-title-main">Monoaminergic activity enhancer</span> Class of compounds in the nervous system

Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of drugs that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs are distinct from monoamine releasing agents (MRAs) like amphetamine and fenfluramine in that they do not induce the release of monoamines from synaptic vesicles but rather potentiate only nerve impulse propagation-mediated monoamine release. That is, MAEs increase the amounts of monoamine neurotransmitters released by neurons per electrical impulse.

<span class="mw-page-title-main">MRZ-9547</span> Dopamine reuptake inhibitor that was under development for fatigue in Parkinsons disease

MRZ-9547, also known as (R)-phenylpiracetam, (R)-phenotropil, or (R)-fonturacetam, is a selective dopamine reuptake inhibitor (IC50Tooltip half-maximal inhibitory concentration = 14.5 μM) that was developed by Merz Pharma. It is the (R)-enantiomer of the racetam and nootropic phenylpiracetam (phenotropil; fonturacetam).

References

  1. 1 2 3 ENSG00000276996 GRCh38: Ensembl release 89: ENSG00000142319, ENSG00000276996 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021609 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Carboni E, Tanda GL, Frau R, Di Chiara G (September 1990). "Blockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminals". Journal of Neurochemistry. 55 (3): 1067–70. doi:10.1111/j.1471-4159.1990.tb04599.x. PMID   2117046. S2CID   23682303.
  6. 1 2 Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, et al. (December 1992). "Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR". Genomics. 14 (4): 1104–6. doi:10.1016/S0888-7543(05)80138-7. PMID   1478653.
  7. 1 2 Schultz W (July 1998). "Predictive reward signal of dopamine neurons". Journal of Neurophysiology. 80 (1): 1–27. doi: 10.1152/jn.1998.80.1.1 . PMID   9658025. S2CID   52857162.
  8. ↑ Torres GE, Gainetdinov RR, Caron MG (January 2003). "Plasma membrane monoamine transporters: structure, regulation and function". Nature Reviews. Neuroscience. 4 (1): 13–25. doi:10.1038/nrn1008. PMID   12511858. S2CID   21545649.
  9. ↑ Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (February 1997). "Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants". The Journal of Neuroscience. 17 (3): 960–74. doi:10.1523/JNEUROSCI.17-03-00960.1997. PMC   6573182 . PMID   8994051.
  10. 1 2 Wheeler DD, Edwards AM, Chapman BM, Ondo JG (August 1993). "A model of the sodium dependence of dopamine uptake in rat striatal synaptosomes". Neurochemical Research. 18 (8): 927–36. doi:10.1007/BF00998279. PMID   8371835. S2CID   42196576.
  11. 1 2 3 4 5 Cameron KN, Solis E, Ruchala I, De Felice LJ, Eltit JM (November 2015). "Amphetamine activates calcium channels through dopamine transporter-mediated depolarization". Cell Calcium. 58 (5): 457–66. doi:10.1016/j.ceca.2015.06.013. PMC   4631700 . PMID   26162812. One example of interest is CaMKII, which has been well characterized as an effector of Ca2+ currents downstream of L-type Ca2+ channels [21,22]. Interestingly, DAT is a CaMKII substrate and phosphorylated DAT favors the reverse transport of dopamine [48,49], constituting a possible mechanism by which electrical activity and L-type Ca2+ channels may modulate DAT states and dopamine release. ... In summary, our results suggest that pharmacologically, S(+)AMPH is more potent than DA at activating hDAT-mediated depolarizing currents, leading to L-type Ca2+ channel activation, and the S(+)AMPH-induced current is more tightly coupled than DA to open L-type Ca2+ channels.
  12. 1 2 Kilty JE, Lorang D, Amara SG (October 1991). "Cloning and expression of a cocaine-sensitive rat dopamine transporter". Science. 254 (5031): 578–9. Bibcode:1991Sci...254..578K. doi:10.1126/science.1948035. PMID   1948035.
  13. ↑ Vaughan RA, Kuhar MJ (August 1996). "Dopamine transporter ligand binding domains. Structural and functional properties revealed by limited proteolysis". The Journal of Biological Chemistry. 271 (35): 21672–80. doi: 10.1074/jbc.271.35.21672 . PMID   8702957.
  14. ↑ Penmatsa A, Wang KH, Gouaux E (November 2013). "X-ray structure of dopamine transporter elucidates antidepressant mechanism". Nature. 503 (7474): 85–90. Bibcode:2013Natur.503...85P. doi:10.1038/nature12533. PMC   3904663 . PMID   24037379.
  15. 1 2 3 4 5 6 7 8 9 10 11 Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". Journal of Neurochemistry. 116 (2): 164–76. doi:10.1111/j.1471-4159.2010.07109.x. PMC   3005101 . PMID   21073468.
  16. 1 2 3 Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Annals of the New York Academy of Sciences. 1216 (1): 86–98. Bibcode:2011NYASA1216...86E. doi:10.1111/j.1749-6632.2010.05906.x. PMC   4183197 . PMID   21272013.
  17. ↑ Sulzer D, Cragg SJ, Rice ME (August 2016). "Striatal dopamine neurotransmission: regulation of release and uptake". Basal Ganglia. 6 (3): 123–148. doi:10.1016/j.baga.2016.02.001. PMC   4850498 . PMID   27141430. Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle. ... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.
  18. ↑ Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G, Mercuri NB (July 2011). "Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front. Syst. Neurosci. 5: 56. doi: 10.3389/fnsys.2011.00056 . PMC   3131148 . PMID   21772817. Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization.
  19. ↑ "TAAR1". GenAtlas. University of Paris. 28 January 2012. Retrieved 29 May 2014.  • tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ventral tegmental area (VTA)
  20. 1 2 Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–416. doi:10.1016/j.neuron.2014.05.043. PMC   4159050 . PMID   25033183. AMPH also increases intracellular calcium (Gnegy et al., 2004) that is associated with calmodulin/CamKII activation (Wei et al., 2007) and modulation and trafficking of the DAT (Fog et al., 2006; Sakrikar et al., 2012).
  21. 1 2 3 Vaughan RA, Foster JD (September 2013). "Mechanisms of dopamine transporter regulation in normal and disease states". Trends in Pharmacological Sciences. 34 (9): 489–96. doi:10.1016/j.tips.2013.07.005. PMC   3831354 . PMID   23968642. AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties [80], although the mechanisms do not appear to be identical for each drug [81]. These processes are PKCβ– and CaMK–dependent [72, 82], and PKCβ knock-out mice display decreased AMPH-induced efflux that correlates with reduced AMPH-induced locomotion [72].
  22. ↑ Ciliax BJ, Drash GW, Staley JK, Haber S, Mobley CJ, Miller GW, et al. (June 1999). "Immunocytochemical localization of the dopamine transporter in human brain". The Journal of Comparative Neurology. 409 (1): 38–56. doi:10.1002/(SICI)1096-9861(19990621)409:1<38::AID-CNE4>3.0.CO;2-1. PMID   10363710. S2CID   46295607.
  23. ↑ Liu Z, Yan SF, Walker JR, Zwingman TA, Jiang T, Li J, et al. (April 2007). "Study of gene function based on spatial co-expression in a high-resolution mouse brain atlas". BMC Systems Biology. 1: 19. doi: 10.1186/1752-0509-1-19 . PMC   1863433 . PMID   17437647.
  24. ↑ Maguire JJ, Davenport AP (19 July 2016). "Trace amine receptor: TA1 receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 22 September 2016.
  25. ↑ Nirenberg MJ, Vaughan RA, Uhl GR, Kuhar MJ, Pickel VM (January 1996). "The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons". The Journal of Neuroscience. 16 (2): 436–47. doi:10.1523/JNEUROSCI.16-02-00436.1996. PMC   6578661 . PMID   8551328.
  26. ↑ Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI (November 1997). "Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra". The Journal of Comparative Neurology. 388 (2): 211–27. doi:10.1002/(SICI)1096-9861(19971117)388:2<211::AID-CNE3>3.0.CO;2-4. PMID   9368838. S2CID   21202901.
  27. ↑ Kawarai T, Kawakami H, Yamamura Y, Nakamura S (August 1997). "Structure and organization of the gene encoding human dopamine transporter". Gene. 195 (1): 11–8. doi:10.1016/S0378-1119(97)00131-5. PMID   9300814.
  28. ↑ Sano A, Kondoh K, Kakimoto Y, Kondo I (May 1993). "A 40-nucleotide repeat polymorphism in the human dopamine transporter gene". Human Genetics. 91 (4): 405–6. doi:10.1007/BF00217369. PMID   8500798. S2CID   39416578.
  29. ↑ Miller GM, Madras BK (2002). "Polymorphisms in the 3'-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression". Molecular Psychiatry. 7 (1): 44–55. doi: 10.1038/sj/mp/4000921 . PMID   11803445.
  30. ↑ Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ (March 2001). "Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism". Journal of Neurochemistry. 76 (5): 1565–72. doi: 10.1046/j.1471-4159.2001.00181.x . PMID   11238740. S2CID   19410051.
  31. ↑ Morón JA, Zakharova I, Ferrer JV, Merrill GA, Hope B, Lafer EM, et al. (September 2003). "Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity". The Journal of Neuroscience. 23 (24): 8480–8. doi:10.1523/JNEUROSCI.23-24-08480.2003. PMC   6740378 . PMID   13679416.
  32. ↑ Pristupa ZB, McConkey F, Liu F, Man HY, Lee FJ, Wang YT, et al. (September 1998). "Protein kinase-mediated bidirectional trafficking and functional regulation of the human dopamine transporter". Synapse. 30 (1): 79–87. doi:10.1002/(SICI)1098-2396(199809)30:1<79::AID-SYN10>3.0.CO;2-K. PMID   9704884. S2CID   20618165.
  33. ↑ Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC (March 2005). "Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors". Genomics. 85 (3): 372–85. doi:10.1016/j.ygeno.2004.11.010. PMID   15718104.
  34. ↑ Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP (March 2009). "International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature". Pharmacological Reviews. 61 (1): 1–8. doi:10.1124/pr.109.001107. PMC   2830119 . PMID   19325074.
  35. ↑ Krause J (April 2008). "SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder". Expert Review of Neurotherapeutics. 8 (4): 611–25. doi:10.1586/14737175.8.4.611. PMID   18416663. S2CID   24589993. Zinc binds at ... extracellular sites of the DAT [103], serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [105,106]. It should be stated that at this time [supplementation] with zinc is not integrated in any ADHD treatment algorithm.
  36. ↑ Sulzer D (February 2011). "How addictive drugs disrupt presynaptic dopamine neurotransmission". Neuron. 69 (4): 628–49. doi:10.1016/j.neuron.2011.02.010. PMC   3065181 . PMID   21338876. They did not confirm the predicted straightforward relationship between uptake and release, but rather that some compounds including AMPH were better releasers than substrates for uptake. Zinc, moreover, stimulates efflux of intracellular [3H]DA despite its concomitant inhibition of uptake (Scholze et al., 2002).
  37. 1 2 Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH (June 2002). "The role of zinc ions in reverse transport mediated by monoamine transporters". The Journal of Biological Chemistry. 277 (24): 21505–13. doi: 10.1074/jbc.M112265200 . PMID   11940571. The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). ... Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET).
  38. ↑ Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (October 2012). "Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses". Journal of the American Academy of Child and Adolescent Psychiatry. 51 (10): 1003–1019.e20. doi:10.1016/j.jaac.2012.08.015. PMID   23021477. With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30 mg/day of zinc were safe for at least 8 weeks, but the clinical effect was equivocal except for the finding of a 37% reduction in amphetamine optimal dose with 30 mg per day of zinc.110
  39. ↑ Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (January 1999). "Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity". Science. 283 (5400): 397–401. Bibcode:1999Sci...283..397G. doi:10.1126/science.283.5400.397. PMID   9888856. S2CID   9629915.
  40. ↑ Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, et al. (March 2001). "Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder". American Journal of Medical Genetics. 105 (2): 145–51. doi:10.1002/1096-8628(2001)9999:9999<::AID-AJMG1161>3.0.CO;2-8. PMID   11304827.
  41. ↑ Yang B, Chan RC, Jing J, Li T, Sham P, Chen RY (June 2007). "A meta-analysis of association studies between the 10-repeat allele of a VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention deficit hyperactivity disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 144B (4): 541–50. doi:10.1002/ajmg.b.30453. PMID   17440978. S2CID   22881996.
  42. ↑ Seymari A, Naseh A, Rezaei S, Salehi Z, Kousha M (January 2024). "The Relationship between Gene SLC6A3 Variable Number of Tandem Repeat (VNTR) and Attention-Deficit/Hyperactivity Disorder". Iranian Journal of Psychiatry. 19 (1): 99–106. doi: 10.18502/ijps.v19i1.14345 . PMC   10896761 . PMID   38420272.
  43. ↑ Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, et al. (February 1997). "Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium". Biological Psychiatry. 41 (3): 299–304. doi:10.1016/S0006-3223(96)00044-3. PMID   9024952. S2CID   42947314.
  44. ↑ Ueno S, Nakamura M, Mikami M, Kondoh K, Ishiguro H, Arinami T, et al. (November 1999). "Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism". Molecular Psychiatry. 4 (6): 552–7. doi: 10.1038/sj.mp.4000562 . PMID   10578237.
  45. ↑ Ueno S (February 2003). "Genetic polymorphisms of serotonin and dopamine transporters in mental disorders". The Journal of Medical Investigation. 50 (1–2): 25–31. PMID   12630565.
  46. ↑ Beaver KM, Wright JP, DeLisi M (September 2008). "Delinquent peer group formation: evidence of a gene x environment correlation". The Journal of Genetic Psychology. 169 (3): 227–44. doi:10.3200/GNTP.169.3.227-244. PMID   18788325. S2CID   46592146.
  47. ↑ Florida State University (2 October 2008). "Specific Gene Found In Adolescent Men With Delinquent Peers". ScienceDaily . Retrieved 8 October 2008.
  48. ↑ Laasonen-Balk T, Kuikka J, Viinamäki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (June 1999). "Striatal dopamine transporter density in major depression". Psychopharmacology. 144 (3): 282–5. doi:10.1007/s002130051005. PMID   10435396. S2CID   32882588.
  49. ↑ Ng J, Zhen J, Meyer E, Erreger K, Li Y, Kakar N, et al. (April 2014). "Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood". Brain. 137 (Pt 4): 1107–19. doi:10.1093/brain/awu022. PMC   3959557 . PMID   24613933.
  50. ↑ Rothman RB, Ananthan S, Partilla JS, Saini SK, Moukha-Chafiq O, Pathak V, et al. (June 2015). "Studies of the biogenic amine transporters 15. Identification of novel allosteric dopamine transporter ligands with nanomolar potency". The Journal of Pharmacology and Experimental Therapeutics. 353 (3): 529–38. doi:10.1124/jpet.114.222299. PMC   4429677 . PMID   25788711.
  51. ↑ Aggarwal S, Liu X, Rice C, Menell P, Clark PJ, Paparoidamis N, et al. (2019). "Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter". ACS Chem Neurosci. 10 (8): 3718–3730. doi:10.1021/acschemneuro.9b00262. PMC   6703927 . PMID   31184115.
  52. ↑ Wersinger C, Sidhu A (April 2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neuroscience Letters. 340 (3): 189–92. doi:10.1016/S0304-3940(03)00097-1. PMID   12672538. S2CID   54381509.
  53. ↑ Lee FJ, Liu F, Pristupa ZB, Niznik HB (April 2001). "Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis". FASEB Journal. 15 (6): 916–26. doi: 10.1096/fj.00-0334com . PMID   11292651. S2CID   3406798.
  54. ↑ Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, et al. (April 2001). "Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1". Neuron. 30 (1): 121–34. doi: 10.1016/S0896-6273(01)00267-7 . PMID   11343649. S2CID   17318937.
  55. ↑ Peck EG, Holleran KM, Curry AM, Holter KM, Estave PM, Sens JP, et al. (August 2024). "Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits". bioRxiv. doi:10.1101/2024.07.27.605436. PMC   11361146 . PMID   39211138.
  56. ↑ Carneiro AM, Ingram SL, Beaulieu JM, Sweeney A, Amara SG, Thomas SM, et al. (August 2002). "The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter". The Journal of Neuroscience. 22 (16): 7045–54. doi:10.1523/JNEUROSCI.22-16-07045.2002. PMC   6757888 . PMID   12177201.
  57. ↑ Midde NM, Yuan Y, Quizon PM, Sun WL, Huang X, Zhan CG, et al. (March 2015). "Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine transport". Journal of Neuroimmune Pharmacology. 10 (1): 122–35. doi:10.1007/s11481-015-9583-3. PMC   4388869 . PMID   25604666.
  58. ↑ Midde NM, Huang X, Gomez AM, Booze RM, Zhan CG, Zhu J (September 2013). "Mutation of tyrosine 470 of human dopamine transporter is critical for HIV-1 Tat-induced inhibition of dopamine transport and transporter conformational transitions". Journal of Neuroimmune Pharmacology. 8 (4): 975–87. doi:10.1007/s11481-013-9464-6. PMC   3740080 . PMID   23645138.
  59. ↑ Purohit V, Rapaka R, Shurtleff D (August 2011). "Drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia". Molecular Neurobiology. 44 (1): 102–10. doi:10.1007/s12035-011-8195-z. PMID   21717292. S2CID   13319355.
  60. 1 2 3 4 Hitri A, Hurd YL, Wyatt RJ, Deutsch SI (February 1994). "Molecular, functional and biochemical characteristics of the dopamine transporter: regional differences and clinical relevance". Clin Neuropharmacol. 17 (1): 1–22. doi:10.1097/00002826-199402000-00001. PMID   8149355.
  61. 1 2 3 4 5 6 7 Schmitt KC, Rothman RB, Reith ME (July 2013). "Nonclassical pharmacology of the dopamine transporter: atypical inhibitors, allosteric modulators, and partial substrates". J Pharmacol Exp Ther. 346 (1): 2–10. doi:10.1124/jpet.111.191056. PMC   3684841 . PMID   23568856.
  62. 1 2 3 4 5 6 7 8 9 10 11 12 Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, et al. (February 2015). "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug Alcohol Depend. 147: 1–19. doi:10.1016/j.drugalcdep.2014.12.005. PMC   4297708 . PMID   25548026.
  63. ↑ Harsing LG, Knoll J, Miklya I (August 2022). "Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum". Int J Mol Sci. 23 (15): 8543. doi: 10.3390/ijms23158543 . PMC   9369307 . PMID   35955676.
  64. ↑ Kostrzewa RM (2022). "Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons". Handbook of Neurotoxicity. Cham: Springer International Publishing. pp. 159–198. doi:10.1007/978-3-031-15080-7_53. ISBN   978-3-031-15079-1.
  65. ↑ Storch A, Ludolph AC, Schwarz J (October 2004). "Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration". J Neural Transm (Vienna). 111 (10–11): 1267–1286. doi:10.1007/s00702-004-0203-2. PMID   15480838.
  66. ↑ Sotnikova TD, Beaulieu JM, Gainetdinov RR, Caron MG (February 2006). "Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter". CNS Neurol Disord Drug Targets. 5 (1): 45–56. doi:10.2174/187152706784111579. PMID   16613553.
  67. ↑ Aceto MD, Botton I, Martin R, Levitt M, Bentley HC, Speight PT (1970). "Pharmacologic properties and mechanism of action of amfonelic acid". Eur J Pharmacol. 10 (3): 344–354. doi:10.1016/0014-2999(70)90206-2. PMID   4393073.
  68. ↑ Porrino LJ, Goodman NL, Sharpe LG (November 1988). "Intravenous self-administration of the indirect dopaminergic agonist amfonelic acid by rats". Pharmacol Biochem Behav. 31 (3): 623–626. doi:10.1016/0091-3057(88)90240-7. PMID   2908003.
  69. ↑ Garattini S (July 1997). "Pharmacology of amineptine, an antidepressant agent acting on the dopaminergic system: a review". Int Clin Psychopharmacol. 12 (Suppl 3): S15–S19. doi:10.1097/00004850-199707003-00003. PMID   9347388.
  70. ↑ Bonnet JJ, Chagraoui A, Protais P, Costentin J (1987). "Interactions of amineptine with the neuronal dopamine uptake system: neurochemical in vitro and in vivo studies". J Neural Transm. 69 (3–4): 211–220. doi:10.1007/BF01244342. PMID   3625193.
  71. ↑ Evans EA, Sullivan MA (2014). "Abuse and misuse of antidepressants". Subst Abuse Rehabil. 5: 107–120. doi: 10.2147/SAR.S37917 . PMC   4140701 . PMID   25187753.
  72. ↑ Haddad P (1999). "Do antidepressants have any potential to cause addiction?". J Psychopharmacol. 13 (3): 300–307. doi:10.1177/026988119901300321. PMID   10512092.
  73. ↑ Dutta AK, Zhang S, Kolhatkar R, Reith ME (October 2003). "Dopamine transporter as target for drug development of cocaine dependence medications". Eur J Pharmacol. 479 (1–3): 93–106. doi:10.1016/j.ejphar.2003.08.060. PMID   14612141.
  74. ↑ Pergolizzi J, Breve F, Magnusson P, LeQuang JA, Varrassi G (February 2022). "Cocaethylene: When Cocaine and Alcohol Are Taken Together". Cureus. 14 (2): e22498. doi: 10.7759/cureus.22498 . PMC   8956485 . PMID   35345678.
  75. ↑ Landry MJ (1992). "An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite". J Psychoactive Drugs. 24 (3): 273–276. doi:10.1080/02791072.1992.10471648. PMID   1432406.
  76. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 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.
  77. 1 2 3 4 5 6 7 Aggarwal S, Mortensen OV (2023). "Discovery and Development of Monoamine Transporter Ligands". Drug Development in Psychiatry. Advances in Neurobiology. Vol. 30. pp. 101–129. doi:10.1007/978-3-031-21054-9_4. ISBN   978-3-031-21053-2. PMC   10074400 . PMID   36928847.
  78. 1 2 3 Tanda G, Hersey M, Hempel B, Xi ZX, Newman AH (February 2021). "Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder". Curr Opin Pharmacol. 56: 13–21. doi:10.1016/j.coph.2020.07.007. PMC   8247144 . PMID   32927246.
  79. ↑ Newman AH, Ku T, Jordan CJ, Bonifazi A, Xi ZX (January 2021). "New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders". Annu Rev Pharmacol Toxicol. 61: 609–628. doi:10.1146/annurev-pharmtox-030220-124205. PMC   9341034 . PMID   33411583.
  80. ↑ Glennon RA, Young R (September 2016). "Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinovalerophenone (α-PVP)". Brain Res Bull. 126 (Pt 1): 111–126. doi:10.1016/j.brainresbull.2016.04.011. PMC   5817884 . PMID   27142261.
  81. ↑ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, et al. (March 2013). "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology. 38 (4): 552–562. doi:10.1038/npp.2012.204. PMC   3572453 . PMID   23072836.
  82. 1 2 3 4 5 6 7 8 Nepal B, Das S, Reith ME, Kortagere S (2023). "Overview of the structure and function of the dopamine transporter and its protein interactions". Front Physiol. 14: 1150355. doi: 10.3389/fphys.2023.1150355 . PMC   10020207 . PMID   36935752.
  83. ↑ Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A, Bahar I (2015). "Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding". Front Neurol. 6: 134. doi: 10.3389/fneur.2015.00134 . PMC   4460958 . PMID   26106364.
  84. ↑ Katz JL, Newman AH, Izenwasser S (July 1997). "Relations between heterogeneity of dopamine transporter binding and function and the behavioral pharmacology of cocaine". Pharmacol Biochem Behav. 57 (3): 505–512. doi:10.1016/s0091-3057(96)00441-8. PMID   9218275.
  85. ↑ Bergman J, France CP, Holtzman SG, Katz JL, Koek W, Stephens DN (December 2000). "Agonist efficacy, drug dependence, and medications development: preclinical evaluation of opioid, dopaminergic, and GABAA-ergic ligands". Psychopharmacology (Berl). 153 (1): 67–84. doi:10.1007/s002130000567. PMID   11255930.
  86. ↑ Izenwasser S, Newman AH, Cox BM, Katz JL (February 1996). "The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter". Eur J Pharmacol. 297 (1–2): 9–17. doi:10.1016/0014-2999(95)00696-6. PMID   8851160.
  87. ↑ White MW, Archer JR (2013). "Pipradrol and Pipradrol Derivatives". Novel Psychoactive Substances. Elsevier. pp. 233–259. doi:10.1016/b978-0-12-415816-0.00010-9. ISBN   978-0-12-415816-0.
  88. 1 2 3 Golovko AI, Bonitenko EY, Ivanov MB, Barinov VA, Zatsepin EP (2016). "The neurochemical bases of the pharmacological activity of ligands of monoamine-transport systems". Neurochemical Journal. 10 (3): 173–183. doi:10.1134/S1819712416030065. ISSN   1819-7124.
  89. 1 2 Hersey M, Bacon AK, Bailey LG, Coggiano MA, Newman AH, Leggio L, et al. (2021). "Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap?". Front Neurosci. 15: 656475. doi: 10.3389/fnins.2021.656475 . PMC   8187604 . PMID   34121988.
  90. ↑ Hauck Newman A, Katz JL (2008). "Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter". Transporters as Targets for Drugs. Topics in Medicinal Chemistry. Vol. 4. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 95–129. doi:10.1007/7355_2008_027. ISBN   978-3-540-87911-4.
  91. 1 2 3 Rothman RB (1994). "A Review of the Effects of Dopaminergic Agents in Humans: Implications for Medication Development". In Erinoff L, Brown RM (eds.). Neurobiological Models for Evaluating Mechanisms Underlying Cocaine Addiction (NIDA Research Monograph 145). U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Drug Abuse. pp. 67–87. Retrieved 4 August 2024.
  92. ↑ Naglich AC, Brown ES, Adinoff B (2019). "Systematic review of preclinical, clinical, and post-marketing evidence of bupropion misuse potential". Am J Drug Alcohol Abuse. 45 (4): 341–354. doi:10.1080/00952990.2018.1545023. PMID   30601027.
  93. ↑ Noe G, Shah K, Ongchuan S, Munjal S (2024). "Clinical Presentations of Bupropion Prescription Drug Misuse: A Systematic Review". J Clin Psychopharmacol. 44 (3): 284–290. doi:10.1097/JCP.0000000000001858. PMID   38656298.
  94. ↑ Aikoye S, Basiru TO, Nwoye I, Adereti I, Asuquo S, Ezeokoli A, et al. (March 2023). "A Systematic Review of Abuse or Overprescription of Bupropion in American Prisons and a Synthesis of Case Reports on Bupropion Abuse in American Prison and Non-prison Systems". Cureus. 15 (3): e36189. doi: 10.7759/cureus.36189 . PMC   10104426 . PMID   37065297.
  95. ↑ Costa R, Oliveira NG, Dinis-Oliveira RJ (August 2019). "Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects". Drug Metab Rev. 51 (3): 293–313. doi:10.1080/03602532.2019.1620763. PMID   31124380.
  96. ↑ Jordan CJ, Cao J, Newman AH, Xi ZX (November 2019). "Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine". Neuropharmacology. 158: 107609. doi:10.1016/j.neuropharm.2019.04.015. PMC   6745247 . PMID   31009632.
  97. 1 2 Hersey M, Bartole MK, Jones CS, Newman AH, Tanda G (July 2023). "Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors". Molecules. 28 (13): 5270. doi: 10.3390/molecules28135270 . PMC   10343811 . PMID   37446929.
  98. 1 2 3 Rothman RB, Glowa JR (1995). "A review of the effects of dopaminergic agents on humans, animals, and drug-seeking behavior, and its implications for medication development. Focus on GBR 12909". Mol Neurobiol. 11 (1–3): 1–19. doi:10.1007/BF02740680. PMID   8561954.
  99. 1 2 3 Salamone JD, Correa M (January 2024). "The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine". Annu Rev Psychol. 75: 1–32. doi:10.1146/annurev-psych-020223-012208. hdl: 10234/207207 . PMID   37788571.
  100. ↑ Kouhnavardi S, Ecevitoglu A, Dragačević V, Sanna F, Arias-Sandoval E, Kalaba P, et al. (June 2022). "A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions". Biomolecules. 12 (7): 881. doi: 10.3390/biom12070881 . PMC   9312958 . PMID   35883437.
  101. ↑ Hersey M, Tanda G (2024). "Modafinil, an atypical CNS stimulant?". Pharmacological Advances in Central Nervous System Stimulants. Adv Pharmacol. Vol. 99. pp. 287–326. doi:10.1016/bs.apha.2023.10.006. ISBN   978-0-443-21933-7. PMID   38467484.
  102. ↑ Böning J, Fuchs G (September 1986). "Nomifensine and psychological dependence--a case report". Pharmacopsychiatry. 19 (5): 386–388. doi:10.1055/s-2007-1017275. PMID   3774872.
  103. ↑ Veinberg G, Vavers E, Orlova N, Kuznecovs J, Domracheva I, Vorona M, et al. (2015). "Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile". Chemistry of Heterocyclic Compounds. 51 (7): 601–606. doi:10.1007/s10593-015-1747-9. ISSN   0009-3122. Phenylpiracetam was originally designed as a nootropic drug for the sustenance and improvement of the physical condition and cognition abilities of Soviet space crews.2 Later, especially during the last decade, phenylpiracetam was introduced into general clinical practice in Russia and in some Eastern European countries. The possible target receptors and mechanisms for the acute activity of this drug remained unclear, until very recently it was found that (R)-phenylpiracetam (5) (MRZ-9547) is a selective dopamine transporter inhibitor that moderately stimulates striatal dopamine release.19
  104. 1 2 Sommer S, Danysz W, Russ H, Valastro B, Flik G, Hauber W (December 2014). "The dopamine reuptake inhibitor MRZ-9547 increases progressive ratio responding in rats". The International Journal of Neuropsychopharmacology. 17 (12): 2045–2056. doi:10.1017/S1461145714000996. PMID   24964269. Here, we tested the effects of MRZ-9547 [...], and its l-enantiomer MRZ-9546 on effort-related decision making in rats. The racemic form of these compounds referred to as phenotropil has been shown to stimulate motor activity in rats (Zvejniece et al., 2011) and enhance physical capacity and cognition in humans (Malykh and Sadaie, 2010). [...] MRZ-9547 turned out to be a DAT inhibitor as shown by displacement of binding of [125I] RTI-55 (IC50 = 4.82 ± 0.05 μM, n=3) to human recombinant DAT expressed in CHO-K1 cells and inhibition of DA uptake (IC50 = 14.5 ± 1.6 μM, n=2) in functional assays in the same cells. It inhibited norepinephrine transporter (NET) with an IC50 of 182 μM (one experiment in duplicate). The potencies for the l-enantiomer MRZ-9546 were as follows: DAT binding (Ki = 34.8 ± 14.8 μM, n=3), DAT function (IC50 = 65.5 ± 8.3 μM, n=2) and NET function (IC50 = 667 μM, one experiment performed in duplicate).
  105. ↑ Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, et al. (September 2017). "S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity". Pharmacology, Biochemistry, and Behavior. 160: 21–29. doi:10.1016/j.pbb.2017.07.009. PMID   28743458. S2CID   13658335.
  106. ↑ Stutz PV, Golani LK, Witkin JM (February 2019). "Animal models of fatigue in major depressive disorder". Physiology & Behavior. 199: 300–305. doi:10.1016/j.physbeh.2018.11.042. PMID   30513290. In a study performed by Sommer et al. (2014), healthy rats treated with the selective dopamine transport (DAT) inhibitor MRZ-9547 (Fig. 1) chose high effort, high reward more often than their untreated matched controls. Unlike similar studies, however, depressive symptoms were not induced before treatment; rather, baseline healthy controls were compared to healthy rats treated with MRZ-9547. [...] In one study, the selective DAT inhibitor MRZ-9547 increased the number of lever presses more than untreated controls (Sommer et al., 2014). The investigators concluded that such effort-based "decision making in rodents could provide an animal model for motivational dysfunctions related to effort expenditure such as fatigue, e.g. in Parkinson's disease or major depression." Based upon the findings with MRZ-9547, they suggested that this drug mechanism might be a valuable therapeutic entity for fatigue in neurological and neuropsychiatric disorders. [...] A high effort bias been reported with bupropion (Randall et al., 2015), lisdexamfetamine (Yohn etal., 2016e), and the DA uptake blockers MRZ-9547 (Sommer et al., 2014), PRX-14040 (Fig. 1) (Yohn et al., 2016d) and GBR12909 (Fig. 1) (Yohn et al., 2016c).
  107. ↑ Dekundy A, Mela F, Hofmann M, Danysz W (June 2015). "Effects of dopamine uptake inhibitor MRZ-9547 in animal models of Parkinson's disease". Journal of Neural Transmission. 122 (6): 809–818. doi:10.1007/s00702-014-1326-8. PMID   25319446.
  108. ↑ Ngo Q, Plante DT (19 September 2022). "An Update on the Misuse and Abuse Potential of Pharmacological Treatments for Central Disorders of Hypersomnolence". Current Sleep Medicine Reports. 8 (4): 147–159. doi:10.1007/s40675-022-00227-4. ISSN   2198-6401.
  109. ↑ Yang J, Gao J (August 2019). "Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy". Expert Rev Clin Pharmacol. 12 (8): 723–728. doi:10.1080/17512433.2019.1632705. PMID   31215815.
  110. ↑ Mikelman SR, Guptaroy B, Schmitt KC, Jones KT, Zhen J, Reith ME, et al. (October 2018). "Tamoxifen Directly Interacts with the Dopamine Transporter". J Pharmacol Exp Ther. 367 (1): 119–128. doi:10.1124/jpet.118.248179. PMC   7250473 . PMID   30108161.
  111. ↑ Schoedel KA, Meier D, Chakraborty B, Manniche PM, Sellers EM (July 2010). "Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users". Clin Pharmacol Ther. 88 (1): 69–78. doi:10.1038/clpt.2010.67. PMID   20520602.
  112. 1 2 3 4 5 6 7 8 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.
  113. 1 2 3 4 5 6 7 Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
  114. ↑ Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo RA, Presby RE (October 2018). "The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation". Pharmacol Rev. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC   6169368 . PMID   30209181.
  115. ↑ Desibhatla M (16 June 2021). "The Development and Evaluation of Novel DA Transport Inhibitors and their Effects on Effort-Related Motivation: A Review". Honors Scholar Theses. Retrieved 10 August 2024.
  116. ↑ Yohn SE, Gogoj A, Haque A, Lopez-Cruz L, Haley A, Huxley P, et al. (September 2016). "Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040". Pharmacol Biochem Behav. 148: 84–91. doi:10.1016/j.pbb.2016.06.004. PMID   27296079.
  117. ↑ Pinterova N, Horsley RR, Palenicek T (2017). "Synthetic Aminoindanes: A Summary of Existing Knowledge". Front Psychiatry. 8: 236. doi: 10.3389/fpsyt.2017.00236 . PMC   5698283 . PMID   29204127.
  118. ↑ Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME (March 2014). "Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives" (PDF). Biochem Pharmacol. 88 (2): 237–244. doi:10.1016/j.bcp.2014.01.024. PMID   24486525.
  119. 1 2 Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC   4211607 . PMID   25193229.
  120. ↑ Banks ML, Bauer CT, Blough BE, et al. (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Exp Clin Psychopharmacol. 22 (3): 274–284. doi:10.1037/a0036595. PMC   4067459 . PMID   24796848.
  121. ↑ Glennon RA, Dukat MG (December 2023). "α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant". ACS Pharmacology & Translational Science. 6 (12): 1780–1789. doi:10.1021/acsptsci.3c00139. PMC   10714429 . PMID   38093842.
  122. ↑ Oeri HE (May 2021). "Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy". Journal of Psychopharmacology. 35 (5): 512–536. doi:10.1177/0269881120920420. PMC   8155739 . PMID   32909493.
  123. 1 2 Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC   4211607 . PMID   25193229.
  124. 1 2 3 Rothman RB, Baumann MH (December 2005). "Targeted screening for biogenic amine transporters: potential applications for natural products". Life Sci. 78 (5): 512–518. doi:10.1016/j.lfs.2005.09.001. PMID   16202429.
  125. 1 2 3 Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, et al. (October 2003). "In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates". J Pharmacol Exp Ther. 307 (1): 138–145. doi:10.1124/jpet.103.053975. PMID   12954796.
  126. ↑ Hutson PH, Pennick M, Secker R (December 2014). "Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug". Neuropharmacology. 87: 41–50. doi:10.1016/j.neuropharm.2014.02.014. PMID   24594478.
  127. ↑ Heal DJ, Cheetham SC, Smith SL (December 2009). "The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety". Neuropharmacology. 57 (7–8): 608–618. doi:10.1016/j.neuropharm.2009.08.020. PMID   19761781.
  128. ↑ Green AR, King MV, Shortall SE, Fone KC (May 2014). "The preclinical pharmacology of mephedrone; not just MDMA by another name". Br J Pharmacol. 171 (9): 2251–2268. doi:10.1111/bph.12628. PMC   3997268 . PMID   24654568.
  129. ↑ Simmons SJ, Leyrer-Jackson JM, Oliver CF, Hicks C, Muschamp JW, Rawls SM, et al. (October 2018). "DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants". ACS Chem Neurosci. 9 (10): 2379–2394. doi:10.1021/acschemneuro.8b00147. PMC   6197900 . PMID   29714473.
  130. 1 2 Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, et al. (April 2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology. 37 (5): 1192–1203. doi:10.1038/npp.2011.304. PMC   3306880 . PMID   22169943.
  131. ↑ Rothman RB, Blough BE, Baumann MH (January 2007). "Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions". AAPS J. 9 (1): E1–10. doi:10.1208/aapsj0901001. PMC   2751297 . PMID   17408232.
  132. 1 2 3 Parker EM, Cubeddu LX (April 1988). "Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding". J Pharmacol Exp Ther. 245 (1): 199–210. PMID   3129549.
  133. ↑ Patrick KS, Markowitz JS (November 1997). "Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder". Human Psychopharmacology: Clinical and Experimental. 12 (6): 527–546. doi:10.1002/(SICI)1099-1077(199711/12)12:6<527::AID-HUP932>3.0.CO;2-U. eISSN   1099-1077. ISSN   0885-6222. S2CID   144548631.
  134. ↑ Nishino S, Mignot E (May 1997). "Pharmacological aspects of human and canine narcolepsy". Prog Neurobiol. 52 (1): 27–78. doi: 10.1016/s0301-0082(96)00070-6 . PMID   9185233. S2CID   31839355.
  135. ↑ Fuller RW, Perry KW, Bymaster FP, Wong DT (March 1978). "Comparative effects of pemoline, amfonelic acid and amphetamine on dopamine uptake and release in vitro and on brain 3,4-dihydroxyphenylacetic acid concentration in spiperone-treated rats". The Journal of Pharmacy and Pharmacology. 30 (3): 197–198. doi:10.1111/j.2042-7158.1978.tb13201.x. PMID   24701.
  136. ↑ Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology. 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC   4194234 . PMID   24800892.
  137. 1 2 Zhao G, Qin GW, Wang J, Chu WJ, Guo LH (January 2010). "Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt". Neurochem Int. 56 (1): 168–176. doi:10.1016/j.neuint.2009.09.015. PMID   19815045.
  138. ↑ Zhang J, Liu X, Lei X, Wang L, Guo L, Zhao G, et al. (November 2010). "Discovery and synthesis of novel luteolin derivatives as DAT agonists". Bioorg Med Chem. 18 (22): 7842–7848. doi:10.1016/j.bmc.2010.09.049. PMID   20971650.
  139. ↑ Rothman RB, Dersch CM, Carroll FI, Ananthan S (March 2002). "Studies of the biogenic amine transporters. VIII: identification of a novel partial inhibitor of dopamine uptake and dopamine transporter binding". Synapse. 43 (4): 268–274. doi:10.1002/syn.10046. PMID   11835522.
  140. 1 2 Pariser JJ, Partilla JS, Dersch CM, Ananthan S, Rothman RB (July 2008). "Studies of the biogenic amine transporters. 12. Identification of novel partial inhibitors of amphetamine-induced dopamine release". J Pharmacol Exp Ther. 326 (1): 286–295. doi:10.1124/jpet.108.139675. PMC   2562894 . PMID   18441249.
  141. 1 2 Rothman RB, Dersch CM, Ananthan S, Partilla JS (May 2009). "Studies of the biogenic amine transporters. 13. Identification of "agonist" and "antagonist" allosteric modulators of amphetamine-induced dopamine release". J Pharmacol Exp Ther. 329 (2): 718–728. doi:10.1124/jpet.108.149088. PMC   2672863 . PMID   19244097.
  142. ↑ Macolino-Kane CM, Ciallella JR, Lipinski CA, Reaume AG (14 July 2017). "Phenotypic Screening". Drug Repositioning. Frontiers in Neurotherapeutics. Boca Raton: CRC Press. pp. 121–145. doi:10.4324/9781315373669-7. ISBN   978-1-315-37366-9.
  143. ↑ Al'tshuler RA (2005). "Comparative Molecular Model Estimation of the Affinity of Phenylethylamines to the Binding Sites of Membrane Transporters". Pharmaceutical Chemistry Journal. 39 (4): 169–175. doi:10.1007/s11094-005-0110-3. ISSN   0091-150X.
  144. ↑ Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, et al. (May 2012). "The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters". J Biol Chem. 287 (22): 18524–18534. doi: 10.1074/jbc.M112.343681 . PMC   3365767 . PMID   22451652.
  145. ↑ Harsing LG, Sershen H, Lajtha A (1994). "Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum". J Neural Transm Gen Sect. 96 (3): 215–225. doi:10.1007/BF01294788. PMID   7826572.
  146. ↑ Wells GB, Lopez MC, Tanaka JC (April 1999). "The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes". Brain Res Bull. 48 (6): 641–647. doi: 10.1016/s0361-9230(99)00053-2 . PMID   10386845.
  147. 1 2 Nguyen H, Cheng MH, Lee JY, Aggarwal S, Mortensen OV, Bahar I (2024). "Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments". Curr Res Physiol. 7: 100125. doi:10.1016/j.crphys.2024.100125. PMC   11148570 . PMID   38836245.
  148. ↑ Aggarwal S, Liu X, Rice C, Menell P, Clark PJ, Paparoidamis N, et al. (August 2019). "Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter". ACS Chem Neurosci. 10 (8): 3718–3730. doi:10.1021/acschemneuro.9b00262. PMC   6703927 . PMID   31184115.
  149. ↑ Aggarwal S, Cheng MH, Salvino JM, Bahar I, Mortensen OV (June 2021). "Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter". Biomedicines. 9 (6): 634. doi: 10.3390/biomedicines9060634 . PMC   8227285 . PMID   34199621.
  150. ↑ Tosh DK, Janowsky A, Eshleman AJ, Warnick E, Gao ZG, Chen Z, et al. (April 2017). "Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters". J Med Chem. 60 (7): 3109–3123. doi:10.1021/acs.jmedchem.7b00141. PMC   5501184 . PMID   28319392.
  151. ↑ Srivastava DK, Navratna V, Tosh DK, Chinn A, Sk MF, Tajkhorshid E, et al. (August 2024). "Structure of the human dopamine transporter and mechanisms of inhibition". Nature. 632 (8025): 672–677. Bibcode:2024Natur.632..672S. doi:10.1038/s41586-024-07739-9. PMC   11324517 . PMID   39112705.
  152. ↑ Rothman RB, Ananthan S, Partilla JS, Saini SK, Moukha-Chafiq O, Pathak V, et al. (June 2015). "Studies of the biogenic amine transporters 15. Identification of novel allosteric dopamine transporter ligands with nanomolar potency". J Pharmacol Exp Ther. 353 (3): 529–538. doi:10.1124/jpet.114.222299. PMC   4429677 . PMID   25788711.
  153. ↑ Moerke MJ, Ananthan S, Banks ML, Eltit JM, Freitas KC, Johnson AR, et al. (November 2018). "Interactions between Cocaine and the Putative Allosteric Dopamine Transporter Ligand SRI-31142". J Pharmacol Exp Ther. 367 (2): 222–233. doi:10.1124/jpet.118.250902. PMC   6170971 . PMID   30150482.
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