• 14. Modulation of Delta(9)-THC-induced increase of cortical and hippocampal acetylcholine release by micro opioid and D(1) dopamine receptors. (nih.gov)
  • In addition, the potency of baclofen to depress EPSCs by GABA-B receptors and the effects of the GABA-uptake inhibitor NO-711 (10 μ m ) were increased in withdrawn rats. (jneurosci.org)
  • In the mid-1970s, Professor Seeman reported a series of studies indicating that the affinity of neuroleptics for dopamine (DA) D 2 receptors correlated highly with their effective clinical dose. (jpn.ca)
  • Removing the tertiary alcohol group in mazindol, a process known as desoxylation, enhances its binding to DAT (Dopamine Transporter) and SERT (Serotonin Transporter) receptors without significantly affecting NET (Norepinephrine Transporter) affinity. (researchem.net)
  • Receptors, Dopamine" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (wakehealth.edu)
  • This graph shows the total number of publications written about "Receptors, Dopamine" by people in this website by year, and whether "Receptors, Dopamine" was a major or minor topic of these publications. (wakehealth.edu)
  • Below are the most recent publications written about "Receptors, Dopamine" by people in Profiles. (wakehealth.edu)
  • The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue. (omeka.net)
  • The drug discrimination paradigm was used to evaluate the contribution of dopamine or serotonin receptors in the mediation of the stimulus properties of ethanol. (omeka.net)
  • Previous results indicate that agents which either decreases synthesis or block postsynaptic dopamine receptors will attenuate the discriminative stimulus produced by d-amphetamine. (omeka.net)
  • On the other hand dopamine additionally acts on dopamine receptors along with its action on α and β adrenergic receptors. (egpat.com)
  • Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward. (nih.gov)
  • When bound to their receptors, opioids cause serotonin and dopamine release , which creates a sense of euphoria and pain relief. (addictionhope.com)
  • A new computational analysis suggests certain dopamine receptors in the brain and body are more complex and dynamic than previously thought, existing in diverse inactive states that only allow the. (nih.gov)
  • Efforts to develop potential pharmacotherapies have led to the identification of a promising lead molecule, JJC8-091, that demonstrates a novel binding mode at the dopamine transporter (DAT). (nih.gov)
  • Troparil is used in scientific research into the dopamine reuptake transporter. (wikipedia.org)
  • A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage and release mechanisms. (eurekamag.com)
  • Cells expressing the dopamine transporter acquired the capacity to take up and release dopamine via the transporter. (eurekamag.com)
  • Dopamine uptake inhibitors had one of three effects on transporter-mediated efflux. (eurekamag.com)
  • The ability to define classes of uptake blockers based on their effects on human transporter-mediated dopamine efflux may lead to the identification of structural features of the transporter that differentiate abused from nonabused drugs. (eurekamag.com)
  • IRP and international researchers led by Amy Hauck Newman, Ph.D. , discovered that R-modafinil, like cocaine, inhibits dopamine uptake, but binds to the dopamine transporter in a unique fashion that may not result in the same addictive response as cocaine. (nih.gov)
  • Thus, we directed our efforts toward designing novel ligands with high affinity and selectivity for the dopamine transporter. (nih.gov)
  • By developing novel compounds with benztropine as the parent ligand, we could make structural and pharmacological comparisons with cocaine and learn more about drug-transporter interactions and how these translate into the behavioral effects of these drugs. (nih.gov)
  • Through these studies, we discovered a novel series of ligands that binds with high affinity to the dopamine transporter and inhibits dopamine uptake. (nih.gov)
  • However, in comparison with cocaine, this series of compounds is selective for the dopamine transporter and is distinct in chemical structure, structure-activity relationships, and behavioral profile. (nih.gov)
  • Based on these findings, we hypothesized that these benztropine-based ligands interact at a binding domain on the dopamine transporter that is different from that of cocaine and may thus lead to behaviors unlike those associated with cocaineuse. (nih.gov)
  • We recently synthesized a novel photoaffinity label that we used in immunologic and proteolytic mapping to demonstrate that, in fact, this ligand labels a binding domain in the 1-2 transmembrane region of the dopamine transporter, rather than the 4-7 transmembrane region labeled by a cocaine-based photoaffinity ligand. (nih.gov)
  • We are also studying other structurally diverse classes of compounds to further characterize the dopamine transporter and other systems that may be related to cocaine abuse, such as the dopamine D3 receptor subtype. (nih.gov)
  • INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo. (abo.fi)
  • LLC-PK1 cells have been stably transfected with cDNAs encoding the human norepinephrine transporter (NET), rat dopamine transporter (DAT), and rat serotonin transporter. (erowid.org)
  • For each cell line expressing a single biogenic amine transporter, efflux of the accumulated substrate was stimulated by amphetamine derivatives, and this efflux was blocked by mazindol, an inhibitor of all three transporters. (erowid.org)
  • The dopamine transporter (DAT)2 mediates reuptake of dopamine from the synaptic cleft and terminates in this way dopaminergic signaling and mediates recycling of released dopamine (1-3). (kipdf.com)
  • Cariprazine, an FDA-approved drug for the treatment of schizophrenia and bipolar disorder, is a high-affinity D3R partial agonist (Ki = 0.22 nM) with 3.6-fold selectivity over the homologous dopamine D2 receptor (D2R). (nih.gov)
  • In the second plenary lecture, Dr. P. Seeman (University of Toronto and Honorary CCNP Fellow) spoke on the "Dopamine hypothesis of schizophrenia and atypical antipsychotic mechanisms. (jpn.ca)
  • The possibility that the atypical neuroleptic olanzapine can antagonize the ability of cocaine to produce both conditioned place preference and self-administration in rats was investigated. (omeka.net)
  • The mechanism(s) underlying the reinforcing, or addictive, effects of cocaine, however, appears to primarily involve the inhibition of dopamine uptake. (nih.gov)
  • the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. (bvsalud.org)
  • 3H-radiolabelled forms of troparil have been used in humans and animals to map the distribution of dopamine transporters in the brain. (wikipedia.org)
  • It is well known that cocaine binds to dopamine, serotonin, and norepinephrine transporters and thereby inhibits reuptake of their respective neurotransmitters. (nih.gov)
  • Neurotransmitters such as dopamine and glutamate are rapidly removed from the synaptic cleft after release, primarily through the actions of neurotransmitter transporters. (nih.gov)
  • The SLC1 family encompasses the five subtypes of the excitatory amino acid transporters (EAATs), and the SLC6 family includes the Na + -dependent transporters for dopamine, serotonin and noradrenaline, also known as the biogenic amine transporters. (nih.gov)
  • In addition, biogenic amine neurotransmitter transporters are the primary targets for therapeutic antidepressants known as reuptake inhibitors, for psychostimulants such as cocaine and amphetamines and for methylphenidate, which is used to treat ADHD. (nih.gov)
  • MEDICINAL CHEMISTRY-SYNTHESIS OF POTENTIAL TREATMENT AGENTS FOR COCAINE ADDICTION Release Date: March 12, 2001 NOTICE: NOT-DA-01-024 RFP AVAILABLE: N01DA-1-8815 National Institute on Drug Abuse The National Institute on Drug Abuse is soliciting proposals from qualified individuals or organizations having the capability to design, synthesize, and scale-up compounds which affect primarily dopaminergic systems and either substitute for cocaine, antagonize its effects, and/or prevent relapse. (nih.gov)
  • Neurochemical studies show that a tyrosine-free amino acid mixture depletes brain tyrosine and decreases dopamine synthesis and release. (ox.ac.uk)
  • Evolutionary selection pressure has favoured the natural synthesis of the cocaine alkaloid. (cocaine.wiki)
  • My research program is currently studying the dopamine and serotonin transport systems and the dopamine D 2 receptor family (D 2 /D 3 ) through the design, synthesis and pharmacological evaluation of novel ligands. (nih.gov)
  • DAT is the principle target for widely abused psychostimulants, such as cocaine and amphetamine (1-3). (kipdf.com)
  • Several new synthetic cathinones, which mimic the effect of classical psychostimulants such as cocaine or MDMA, have appeared in the global illicit drug market in the last decades. (iqs.edu)
  • Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. (wakehealth.edu)
  • Highly selective dopamine D3 receptor (D3R) partial agonists/antagonists have been developed for the treatment of psychostimulant use disorders (PSUD). (nih.gov)
  • WELLBUTRIN XL (bupropion hydrochloride), an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. (theodora.com)
  • Antidepressants include selective serotonin re-uptake inhibitors (SSRIs), such as fluoxetine, and tricyclic antidepressants, such as amitriptyline. (addictionhope.com)
  • Serotonin-mediated increase in prefrontal cortex dopamine release: pharmacological characterization. (aspetjournals.org)
  • Molecular and preclinical pharmacological findings support translation of R-modafinil studies to clinical trials in the cocaine-abusing population as a potential treatment. (nih.gov)
  • but cocaine is an even more potent re-uptake inhibitor of the insect-specific neurotransmitter octopamine . (cocaine.wiki)
  • Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide): Consider dose reduction when using with CONTRAVE. (nih.gov)
  • Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine, and does not inhibit monoamine oxidase. (theodora.com)
  • Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with bupropion hydrochloride tablets or within 14 days of stopping treatment with bupropion hydrochloride tablets. (nih.gov)
  • It is also used for animal research into stimulant drugs as an alternative to cocaine which produces similar effects, but avoids the stringent licensing requirements for the use of cocaine itself. (wikipedia.org)
  • The legal status of troparil and many other cocaine analogs in Canada, is dependent on if ecgonine, coca, or cocaine were derivatives of the compound, according to the wording on the entry of coca in Schedule 1 of the Controlled Drugs and Substances Act. (wikipedia.org)
  • She denied use of any drugs of abuse in the previous few days, although her urine was positive for cannabinoids and cocaine metabolites. (nih.gov)
  • Some drugs, in addition to inhibiting uptake, inhibited spontaneous release of dopamine. (eurekamag.com)
  • All of the drugs with the potential for abuse by humans either enhanced release (methamphetamine, amphetamine, and ethanol) or had no effect on release (phencyclidine, cocaine, and WIN 35,428). (eurekamag.com)
  • 3. Differences in dopamine responsiveness to drugs of abuse in the nucleus accumbens shell and core of Lewis and Fischer 344 rats. (nih.gov)
  • 5. A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs: a brain dialysis study in Roman high- and low-avoidance rats. (nih.gov)
  • 19. Dopamine responsiveness to drugs of abuse: A shell-core investigation in the nucleus accumbens of the mouse. (nih.gov)
  • Cocaine is one of the most commonly abused drugs in the United States, especially in urban areas. (medscape.com)
  • Drugs like TCAs and MAO inhibitors are not specific for adrenergic neurons but also act on serotoninergic and dopaminergic neurons. (egpat.com)
  • These results suggest that, unlike cocaine, an increased physical response requirement can decrease nicotine intake. (nih.gov)
  • We reported here that 6-month E-CIG vapor containing nicotine inhalation decreased dopamine concentration only in the STR. (frontiersin.org)
  • Troparil is a few times more potent than cocaine as a dopamine reuptake inhibitor, but is less potent as a serotonin reuptake inhibitor, and has a duration spanning a few times longer, since the phenyl ring is directly connected to the tropane ring through a non-hydrolyzable carbon-carbon bond. (wikipedia.org)
  • Our results demonstrated that all tested synthetic cathinones are potent dopamine (DA) uptake inhibitors, especially the N-ethyl analogs, while the ring-substituted cathinones tested showed higher potency as SERT inhibitors than their no ring-substituted analogs. (iqs.edu)
  • Tyrosine depletion attenuates the behavioural stimulant effects of amphetamine and cocaine in rats. (ox.ac.uk)
  • The purpose of this study was to examine whether first training rats to discriminate the stimulus cues produced by an indirect dopamine agonist, cathinone, would influence a subsequent test of preference. (omeka.net)
  • This study investigated the ability of bilateral excitotoxic lesions of the basolateral amygdala (BLA) to disrupt cocaine self-administration, responding during extinction sessions, and stimulus cued recovery of extinguished responding in rats. (omeka.net)
  • Two groups of N/Nih male rats were trained to discriminate saline vehicle from either 2.0 mg/kg (n = 10) or 10.0 mg/kg (n = 10) cocaine in a food-motivated, two-lever operant paradigm. (omeka.net)
  • However, because of its chemical nature, high concentrations of cocaine are expected in milk. (nih.gov)
  • Cocaine breastmilk concentrations have varied over 100-fold in these reports. (nih.gov)
  • Ecgonine methyl ester was usually not detected and only traces of norcocaine were detected unless cocaine concentrations were very high. (nih.gov)
  • Breastmilk cocaine concentrations ranged from 24.4 to 38.5 mcg/L with an average of 32.4 mcg/L. Benzoylecgonine concentrations ranged from 17.6 to 91.2 mcg/L with an average concentration of 53.5 mcg/L. The ratios of cocaine to benzoylecgonine varied, possibly related to the time of cocaine ingestion prior to breastmilk sampling. (nih.gov)
  • We tested the hypothesis that Mn concentration in the central nervous system (CNS), particularly in the ventral mesencephalon, is decreased by inhibiting dopamine reuptake using cocaine or by decreasing dopamine concentrations using reserpine. (nih.gov)
  • Ionic conditions that stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low concentrations of extracellular Na+, were found to stimulate Ca(2+)-independent release of [3H]dopamine from transfected COS-7 cells. (eurekamag.com)
  • Other inhibitors of transport, such as cocaine, mazindol, citalopram, and nisoxetine, failed to stimulate efflux from these cells at concentrations that inhibited influx. (erowid.org)
  • Reserpine: non-selective blockade of vesicular uptake and storage of biogenic amines. (pharmacology2000.com)
  • Both of these compounds are markers for concurrent use of cocaine and alcohol. (nih.gov)
  • The major goal of this project is to provide NIDA with a resource of novel compounds, and compounds in sufficient quantities for testing, which have potential use in the treatment of cocaine abuse. (nih.gov)
  • Specifically, animals treated with these dopamine-uptake inhibitors do not demonstrate cocaine-like behavior typical of psychostimulant abuse, and some of the compounds attenuate cocaine-induced behaviors. (nih.gov)
  • Medication-assisted treatments are unavailable to patients with cocaine use disorders. (nih.gov)
  • Furthermore, Mazindol holds patents for various applications, including the treatment of schizophrenia, reducing cravings associated with cocaine use, and managing neurobehavioral disorders. (researchem.net)
  • We hope that by elucidating mechanisms underlying the reinforcing effects of cocaine, through the use of precise molecular probes, we may ultimately be able to design therapeutics for the treatment of cocaine abuse. (nih.gov)
  • Other derivatives were much less effective at stimulating efflux than at inhibiting uptake. (erowid.org)
  • Constitutively internalized wild type DAT probed with the fluorescently tagged cocaine analogue JHC 1-64, exhibited the same co-localization pattern as TacDAT in 1Rb3An27 cells and in cultured midbrain dopaminergic neurons. (kipdf.com)
  • The regulation of glutamate (Glu) release from the excitatory input to dopamine cells in the ventral tegmental area (VTA) during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. (jneurosci.org)
  • Inhibition of glutamate release during acute withdrawal would add to the inhibition of dopamine cells that is mediated by an augmented release of GABA ( Bonci and Williams, 1997 ). (jneurosci.org)
  • Presynaptic regulation of glutamate release from these excitatory synapses by opioids has not been investigated and could be important in shaping the pattern of activity of dopamine cells. (jneurosci.org)
  • II: Cocaine or reserpine inhibit manganese concentration in the rat brain. (nih.gov)
  • Cocaine or reserpine decreased the Mn concentration in the ventral mesencephalon, occipital pole, frontal lobe and caudate putamen but did not change the Mn concentration in the cerebellum. (nih.gov)
  • The results indicate that the mechanism(s) by which Mn is concentrated in many brain regions can be inhibited by cocaine, a dopamine reuptake inhibitor, or by reserpine, a dopamine depleter, and suggest that the Mn concentration in the CNS is related to dopamine reuptake and/or concentration. (nih.gov)
  • Cocaine addiction is a chronic and relapsing disorder that affects millions worldwide The Lancet - Addiction , exerting a toll in lives lost, families torn, and communities destroyed. (nih.gov)
  • No medications are currently available to treat cocaine addiction. (nih.gov)
  • The introduction and widespread use of crack cocaine in the 1980s, the severity of the addiction, and comorbid problems prompted the scientific community to investigate treatment options. (netce.com)
  • W e have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. (biopsychiatry.com)
  • Human embryonic kidney (HEK293) cells expressing the human isoforms of SERT and DAT were used for the uptake inhibition and release assays. (iqs.edu)
  • According to an ELISA-based assay, TacDAT intracellular accumulation was increased by the lysosomal protease inhibitor leupeptin and by monensin, an inhibitor of lysosomal degradation and recycling. (kipdf.com)
  • Effects of napsagatran (Ro 46-6240), a new synthetic thrombin inhibitor and of heparin in a canine model of coronary artery thrombosis: comparison with an ex vivo annular perfusion chamber model. (aspetjournals.org)
  • Our initial synthetic studies were based on structural modification of a known dopamine-uptake inhibitor and treatment for Parkinson s disease, benztropine. (nih.gov)
  • Apparently, it was their intention to separate the stimulant actions of cocaine from its toxicity and dependence liability. (wikipedia.org)
  • Troparil has similar effects to cocaine in animal studies, but recreational use of this compound to date has proven extremely rare. (wikipedia.org)
  • This molecule shares several structural features with both cocaine and another known dopamine-uptake inhibitor, GBR 12909, but does not show reinforcing effects in animal models of drug abuse. (nih.gov)
  • Olanzapine attenuates the reinforcing effects of cocaine. (omeka.net)
  • These findings provide behavioural evidence that tyrosine-free amino acid mixtures reduce presynaptic dopamine function in the brain. (ox.ac.uk)
  • These results suggest that one of the consequences of withdrawal from chronic morphine is an enhanced presynaptic inhibition of the excitatory inputs to the dopamine cells of the VTA. (jneurosci.org)
  • Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. (wakehealth.edu)
  • This uptake process is not only essential for the termination of neurotransmission, but also serves to reestablish the intracellular levels of the neurotransmitters for subsequent release. (nih.gov)