Substrates dopamine transporter dopamine uptake inhibitors. Medical search. Frequent questions

Development of 3-Phenyltropane Analogues with High Affinity for the Dopamine and Serotonin Transporters and Low Affinity for the Norepinephrine Transporter. (acs.org)
mIBG enters cancer cells through the norepinephrine transporter (NET) where the radioactive decay of 131 I causes DNA damage, cell death, and tumor necrosis. (aspetjournals.org)
Norepinephrine transporter, organic cation transporters, and multidrug and toxin extrusion proteins play differential roles in tumor targeting, systemic elimination, and accumulation in normal tissues. (aspetjournals.org)
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 . (cloudfront.net)

Transcellular uptake of lipophilic drug compounds is limited by the activity of active efflux pumps in the luminal membrane. (ku.dk)
As a result, the majority of registered CNS drug compounds are small lipophilic compounds which are not efflux transporter substrates. (ku.dk)
Since efflux pump activity is limiting drug uptake, it has been investigated whether coadministration of drug compounds with efflux pump inhibitors could increase drug uptake. (ku.dk)
Therefore, we hypothesized Inhibitors,Modulators,Libraries that the estrogen mediated changes in dopamine efflux that we have observed may involve similar mechanisms. (inhibitorkit.com)
In this study we exam ined both indirect and direct mechanisms involved in physiological estrogen mediated dopamine efflux in Inhibitors,Modulators,Libraries con junction with the cellular location of the ERs and the DAT. (inhibitorkit.com)
Then we addressed the subcellular localization of ER, ER, the alternative mem brane ER, and DAT to see if estrogen induced trafficking of these proteins in and out of the plasma membrane could explain some of the regulatory effects on dopamine efflux. (inhibitorkit.com)
Transporter-mediated monoamine efflux was assessed in HEK 293 cells stably expressing the respective transporter as previously described. (mephedrone.com)
Monoamine transporter blockers were included in the experiment to determine "pseudo-efflux" caused by nonspecific monoamine release and subsequent reuptake inhibition. (mephedrone.com)
Intracellular iron levels are elaborately balanced by iron efflux, uptake, and storage proteins that are regulated by iron regulatory proteins (IRPs, including IRP1 and IRP2) [ 16 ]. (nature.com)
[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. (cloudfront.net)

Nonspecific uptake in the presence of selective inhibitors was subtracted from the total counts. (mephedrone.com)

Progressive loss of nigrostriatal dopamine (DA) neurons is the neuropathological hallmark of Parkinson's disease (PD). (jneurosci.org)
Preliminary evidence suggests that the dopamine transporter couples to L-type voltage-gated calcium channels (particularly Ca v 1.2 and Ca v 1.3 ), which are expressed in virtually all dopamine neurons. (cloudfront.net)
[11] As a result of DAT-Ca v 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. (cloudfront.net)
A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. (biomedcentral.com)
In the resting state, the synthesized DA is transported into and stored in vesicles by vesicular monoamine transporter 2 (VMAT2) in the cytosol of dopaminergic neurons, facilitated by a vesicular ATPase-dependent H + gradient. (biomedcentral.com)
A key problem for dopaminergic neurons is the duality of dopamine as a signal required for neural computation and a toxin as its oxidation produces free radicals. (buffalo.edu)

Human being dopamine (DA) transporter (hDAT) regulates dopaminergic signaling in the central nervous system by maintaining the synaptic concentration of DA at physiological levels upon reuptake of DA into presynaptic terminals. (cancerdir.com)
The human dopamine transporter (hDAT), one member of a family of Na + /Cl - dependent transmembrane transport proteins, serves as a critical regulator of dopaminergic neurotransmission throughout much of the brain. (biomedcentral.com)

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. (cloudfront.net)

There is some, albeit mixed, in vitro evidence that the antidepressant and modestly selective DRI amineptine may in addition to inhibiting the reuptake of dopamine selectively induce the presynaptic release of dopamine without affecting that of norepinephrine or serotonin. (wikipedia.org)
4-MA and d-amphetamine exhibited comparable potencies as releasers of norepinephrine (NE) and dopamine (DA), but 4-MA was a more powerful releaser of serotonin in a research evaluating the monoamine releasing potencies of a series of amphetamine analogs in vitro (5-HT). (mephedrone.com)
Fluoxetine and norfluoxetine appear to be in the in vitro setting potent inhibitors of two primary cytochrome P450 microsomal enzyme isoforms, CYP2D6 and CYP3A4. (pharmacology2000.com)
Flp recombinase, the enzymatic basis of the system, is a Saccharomyces cerevisiae derived enzyme that utilizes a substrate Flp recombination target (FRT) sequence upstream of a gene of interest (GOI) to site-specifically insert the GOI into a target site in a host cell line, thereby providing a well-controlled approach to establishing the in vitro functional effect of the DAT1 VNTR polymorphism on the DAT [ 37 ]. (biomedcentral.com)

A number of specific cytochrome P450 microsomal enzyme isoforms have been identified as important for antidepressant metabolism, including those classified as serotonin selective reuptake inhibitors (SSRIs). (pharmacology2000.com)
In 2000, the regulatory ball got rolling with a letter of the European Commission to the Committee for Proprietary Medicinal Products (CPMP) requesting a review of the potential for dependency/withdrawal reactions of selective serotonin reuptake inhibitors. (clinicalleader.com)

Some CNS drug compounds enter the brain via nutrient transport proteins, an example is the levodopa, a prodrug of Dopamine, which crosses the BBB via the large neutral amino acid transporter LAT1. (ku.dk)
In particular, human organic cation transporter 2 (hOCT2) and multidrug and toxin extrusion proteins 1 and 2-K (hMATE1/2-K) likely mediate renal secretion of mIBG, whereas hOCT1 and hOCT3 may contribute to mIBG uptake into normal tissues such as the liver, salivary glands, and heart. (aspetjournals.org)
The plasma membrane can be envisioned as a central compartment in the cellular adaptation to diverse stress conditions as it shapes the interactions between cells and their environment by harboring an elaborate complement of transmembrane proteins, e.g. transporters, channels, receptors, or adhesion proteins. (cell-stress.com)
These cell surface proteins impinge on the vast majority of all cellular functions by mediating nutrient uptake, preserving ion homeostasis and initiating complex signaling cascades in response to extracellular cues. (cell-stress.com)

It is particularly of note that the mechanism of action at the dopamine transporter (DAT) for dopamine releasers/substrates is entropy-driven (i.e. hydrophobic), whereas for dopamine re-uptake inhibitors it is enthalpy-driven (i.e. conformational change). (wikipedia.org)
The use of a single high concentration and the release durations were based on kinetic evaluation of the release-over-time curves for substrate-releasers in previous studies. (mephedrone.com)

It has been demonstrated that MMAI has similar effects on the SERT to MDMA and a strong selectivity for 5-HT uptake inhibition vs. NE and DA uptake inhibition. (mephedrone.com)
H(2)(15)O]-Positron Emission Tomography (PET) was used to examine regional cerebral blood flow (rCBF) after administration of a single oral dose of the serotonin realeaser and uptake inhibitor MDMA (1.7 mg/kg) or placebo to 16 MDMA-naïve subjects. (researchgate.net)

Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH (1997) Sex differences in dopamine receptor overproduction and elimination. (springer.com)
Andersen SL, Thompson AT, Rutstein M, Hostetter JC, Teicher MH (2000) Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats. (springer.com)
We compared a novel series of mephedrone analogs and related designer medicines to mephedrone in the current investigation by analyzing the monoamine transporter and receptor interaction characteristics of each (Figure 1). (mephedrone.com)
Other drugs which serve as substrates (non-antidepressant agents) for CYP1A2 include caffeine, theophylline, phenacetin and propranolol which is classified as a nonselective β-adrenergic receptor antagonist. (pharmacology2000.com)

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. (cloudfront.net)

We studied the involvement of protein kinases A and C, phospho inositol 3 kinase, extracellu lar regulated kinases , vesicular release of dopamine, and changes in intracellular Ca2 concentra tions in the actions of estrogens. (inhibitorkit.com)
Once dopamine binds, the protein undergoes a conformational change, which allows both sodium and dopamine to unbind on the intracellular side of the membrane. (cloudfront.net)

The initial determination of the membrane topology of DAT was based upon hydrophobic sequence analysis and sequence similarities with the GABA transporter. (cloudfront.net)

This creates an environment for increased rapid bioavail ability of E2 which can elicit nongenomic effects such as Ca2 mobilization, kinase activation, and alterations in dopamine subcellular location via membrane estrogen receptors. (inhibitorkit.com)
Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors. (illumina.com)
It performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine, or by uptake by surrounding cells. (wikidoc.org)

While carrier-mediated transport of drug compounds may seem attractive, the development of drugs targeting transporters is very challenging, since the compounds should have a good fit to the binding site, while still maintaining their CNS target affinity. (ku.dk)

Substrate specificity of catechol oxidase from Lycopus europaeus and characterization of the bioproducts of enzymic caffeic acid oxidation. (lookformedical.com)
The substrate specificity of catechol oxidase from Lycopus europaeus towards phenols is examined. (lookformedical.com)

In the cytosol, other transporters sequester the dopamine into vesicles for storage and later release. (cloudfront.net)

Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: Neural and neurochemical substrates. (springer.com)
This study provides first indications for an underlying neurochemical pathomechanism involving the dopamine system of PCB-related deterioration of fine motor performance regarding accuracy. (chromsystems.com)

The dopamine transporter ( DAT ) also ( sodium-dependent dopamine transporter ) is a membrane-spanning protein coded for in the human by the SLC6A3 gene , (also known as DAT1 ), that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol . (cloudfront.net)

Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. (illumina.com)

In the synaptosomes of the rat brain, it has been demonstrated that 5-IT is a substrate for the transporters for norepinephrine (NET), dopamine (DAT), and serotonin (SERT), with increased potency for release at NET and DAT over SERT. (mephedrone.com)
Inhibitors of the serotonin transporter protein (SERT): the design and synthesis of biotinylated derivatives of 3-(1, 2, 3, 6-tetrahydro-pyridin-4-yl)-1H-indoles. (google.nl)

A physiological mathematical model of chronic myeloid leukemia, validated by experiments in transgenic mice and clinical data, identifies mechanisms underlying the response to tyrosine kinase inhibitor therapy, predicts biomarkers of primary resistance, and suggests new strategies to improve treatment outcomes. (elifesciences.org)
inhibit the latest tyrosine and transporters from MIT Professional Education. (erik-mill.de)

Prolyl oligopeptidase (PREP) is a peptidase enzyme that has several substrates. (helsinki.fi)

Although vitamin D can enhance the absorption, especially under conditions of dietary phosphate depletion, intestinal phosphate absorption does not require the presence of active vitamin D. Specifically, high serum phosphate and high dietary phosphate intake do not significantly impair intestinal uptake. (medscape.com)

Modifications Inhibitors,Modulators,Libraries in the phosphorylation state of the DAT by kinases causes alterations in the function and location of the DAT. (inhibitorkit.com)

Gentamycin sulfate Number 1 Molecular dynamics (MD) setup for simulating the connection of DAT with dopamine (DA) orphenadrine (ORPH) and amphetamine (AMPH). (cancerdir.com)
Further, evidence suggests that adolescent amphetamine exposure alters monoamine signaling and increases sensitivity to drugs that act on dopamine, norepinephrine, and serotonin later in life. (springer.com)
Boomhower SR, Newland MC (2019) d-Amphetamine and methylmercury exposure during adolescence alters sensitivity to monoamine uptake inhibitors in adult mice. (springer.com)

Paracellular brain uptake of drug compounds is limited by the physical tightness of the endothelium, which is tightly sealed with junction complexes. (ku.dk)

Dopamine underlies several aspects of cognition, including reward, and DAT facilitates regulation of that signal. (cloudfront.net)

In coenzyme A, the business end is the thiol group that becomes bound to the substrate, and in NAD + it is the nicotinamide moiety that undergoes reversible reduction and oxidation. (heresy.is)
This markedly increases dopamine oxidation and oxidative stress. (buffalo.edu)

Synthesis, Fluorine-18 Radiolabeling, and Biological Evaluation of N-((E)-4-Fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4′-halophenyl)nortropanes: Candidate Radioligands for In Vivo Imaging of the Brain Dopamine Transporter with Positron Emission Tomography. (acs.org)

A 40-bp variable number of tandem repeats (VNTR) polymorphism exists in the 15th exon of DAT1 , the gene encoding the human dopamine transporter (DAT). (biomedcentral.com)

Emerging evidences suggest that the polyspecific organic cation transporters play important roles in systemic disposition and tissue-specific uptake of mIBG. (aspetjournals.org)
Emerging evidences suggest that the polyspecific organic cation transporters are the major transporters driving the systemic elimination and tissue-specific disposition of mIBG in normal organs. (aspetjournals.org)
Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction. (medscape.com)

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. (cloudfront.net)
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. (cloudfront.net)

These inhibitors have therapeutic application in the treatment of cancer and inflammatory diseases such as rheumatoid arthritis. (jak1inhibitor.com)

The much more unstable bipedal movement may require more dopamine, which supports the neural computation necessary for movement. (buffalo.edu)

Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron. (medscape.com)

These agents improve peripheral glucose uptake and utilization. (medscape.com)

Black defects of spontaneous echo contrast are completely Inhibitors,research,lifescience,medical same region shown as mild mitral regurgitation in color Doppler imaging (Fig. 1D vs. C, F vs. E, and Supplementary movie 1). (anti-cancers.com)
Mild mitral regurgitation was clearly … This patient Inhibitors,research,lifescience,medical showed severe spontaneous echo contrast in her left atrium. (anti-cancers.com)
Mutations of parkin cause increased spontaneous release of dopamine and reduced dopamine uptake, thereby disrupting the precision of dopaminergic transmission. (buffalo.edu)

Inhibition of the human NE, DA, and 5-HT transporter was assessed in human embryonic kidney (HEK) 293 cells stably transfected with the respective human transporter as previously described. (mephedrone.com)

Transporters on the plasma membrane of tumor cells are promising molecular "Trojan horses" to deliver drugs and imaging agents into cancer cells. (aspetjournals.org)
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. (cloudfront.net)
The driving force for DAT-mediated dopamine reuptake is the ion concentration gradient generated by the plasma membrane Na + /K + ATPase . (cloudfront.net)

Despite its selective uptake by neuroendocrine tumors, mIBG accumulates in several normal tissues and leads to tissue-specific radiation toxicities. (aspetjournals.org)
The clinical use of mIBG as a radiopharmaceutical in cancer diagnosis and treatment can be further improved by taking a holistic approach considering mIBG transporters in both cancer and normal tissues. (aspetjournals.org)
Hence, a major goal in cancer drug development and therapy is to increase tumor-specific drug uptake while reducing uptake into normal tissues to minimize toxicities. (aspetjournals.org)

peripheral insulin-stimulated uptake is increased. (medscape.com)

Parameterizations of Substrate/Medications Dopamine AMPH cocaine or ORPH all carry +1 charge. (cancerdir.com)

During the adolescent period, monoamine neurotransmitter systems (particularly dopamine, norepinephrine, and serotonin) undergo continued development, and evidence from experimental animal models suggests that repeated use of amphetamines during this time can impact behavioral processes that rely on monoamine systems throughout the lifespan. (springer.com)

This mini-review focuses on the clinical applications of mIBG in neuroendocrine cancers and the differential roles of NET, OCT, and MATE transporters in mIBG disposition, response and toxicity. (aspetjournals.org)

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain. (wikipedia.org)
Serotonin-dopamine releasing agents are much rarer and are not selective for monoamine release. (wikipedia.org)
In addition, the transporter may contribute to dopamine release when the neuron depolarizes. (cloudfront.net)

Two experiments were performed on regular HEK-cells: inhibitor experiment with KYP-2047 (1 or 10 µM) and overexpression experiment (transfection with either active or inactive hPREP plasmid). (helsinki.fi)

A closely related type of drug is a dopamine reuptake inhibitor (DRI). (wikipedia.org)

The most selective dopamine releaser is 4-methylaminorex, but it also has considerable activity as a norepinephrine releaser. (wikipedia.org)
Monoamine releasing agent Norepinephrine-dopamine releasing agent Serotonin-dopamine releasing agent Serotonin-norepinephrine-dopamine releasing agent Stimulant Nootropic Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. (wikipedia.org)

Anatomy21

Organisms7

Diseases9

Chemicals and Drugs138

Analytical, Diagnostic and Therapeutic Techniques and Equipment19

Psychiatry and Psychology10

Phenomena and Processes32

Disciplines and Occupations1

Information Science3

Health Care1

Norepinephrine Transporter4

Efflux10

Selective inhibitors1

Neurons6

HDAT2

Monoamine transporters1

Vitro4

Reuptake inhibitors2

Proteins4

Releasers2

MDMA2

Receptor4

Genetic polymorphism1

Intracellular2

Hydrophobic1

Receptors3

Affinity1

Specificity2

Vesicles1

Neurochemical2

Cytosol1

Metabolism and clearance1

SERT2

Tyrosine2

Enzyme1

Intestinal1

Phosphorylation1

Amphetamine3

Sealed with jun1

Regulation1

Oxidation2

Vivo1

DAT11

Systemic3

Sodium2

Therapeutic1

Neural1

Antidepressants1

Glucose1

Spontaneous3

Kidney1

Membrane3

Tissues3

Peripheral1

Medications1

Suggests1

Toxicity1

Release3

Experiment1

Drug1

Activity2