ArticleProceedings of the National Academy of Sciences of the United States of America2009
The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
130 citing papers in PubMed, 247 citations in OpenAlex.
- Effect of TAAR1/5-HTTranslational psychiatry · 2021Trial
- Structure based discovery of antipsychotic-like TAAR1 agonists.Nature communications · 2026Article
- Novel Insights into the Pleiotropic Neuroprotective Action of Synthetic Halogen Free Thyronamine-like Analogues.Molecules (Basel, Switzerland) · 2026Article
- Novel selective morpholine trace amine-associated receptor 1 partial agonists show promising preclinical effects for neuropsychiatric disorders and are well tolerated in healthy volunteers.Molecular psychiatry · 2026Article
- A potential role for trace amines in the treatment of septic shock.Journal of intensive medicine · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- TAAR1-mediated pathways regulating nigrostriatal function and the discovery and pharmacological characterization of a novel TAAR1 agonist, Selutaront.Frontiers in pharmacology · 2026Article
- Potential of Small Molecule TAAR-1 Agonists for the Therapy of Neurodegenerative Psychosis: A Medicinal Chemistry Perspective.Mini reviews in medicinal chemistry · 2026Review
- The Role of Trace Amine-Associated Receptor 1 (TAAR1) in the Pathophysiology and Treatment of Depression.Current neuropharmacology · 2026Review
- TAAR1 deficiency impairs mitochondrial dynamics and synaptic integrity in the medial prefrontal cortex and associated cognition in mice.Translational psychiatry · 2025Article
- Trace Amine-associated Receptors (TAARs): Candidate Targets in the Treatment of Bipolar Disorders.Actas espanolas de psiquiatria · 2025Review
- Trace amine-associated receptor 1 agonists differentially regulate dopamine transporter function.Molecular pharmacology · 2025Article
- Trace amine-associated receptor 1 (TAAR1): an emerging therapeutic target for neurodegenerative, neurodevelopmental, and neurotraumatic disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Regulation by Trace Amine-Associated Receptor 1 (TAAR1) of Dopaminergic-GABAergic Interaction in the Striatum: Effects of the Enhancer Drug (-)BPAP.Neurochemical research · 2025Article
- Molecular Mechanisms of Methamphetamine-Induced Addiction via TAAR1 Activation.Journal of medicinal chemistry · 2024Article
- Wakefulness Induced by TAAR1 Partial Agonism in Mice Is Mediated Through Dopaminergic Neurotransmission.International journal of molecular sciences · 2024Article
- Wakefulness Induced by TAAR1 Partial Agonism is Mediated Through Dopaminergic Neurotransmission.bioRxiv : the preprint server for biology · 2024Article
- Dopamine D1 receptor in medial prefrontal cortex mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- TAAR1 agonist ulotaront modulates striatal and hippocampal glutamate function in a state-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Trace Amine-Associated Receptors' Role in Immune System Functions.Biomedicines · 2024Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) that is nonselectively activated by endogenous metabolites of amino acids. TAAR1 is considered a promising drug target for the treatment of psychiatric and neurodegenerative disorders. However, no selective ligand to identify TAAR1-specific signaling mechanisms is available yet. Here we report a selective TAAR1 antagonist, EPPTB, and characterize its physiological effects at dopamine (DA) neurons of the ventral tegmental area (VTA). We show that EPPTB prevents the reduction of the firing frequency of DA neurons induced by p-tyramine (p-tyr), a nonselective TAAR1 agonist. When applied alone, EPPTB increases the firing frequency of DA neurons, suggesting that TAAR1 either exhibits constitutive activity or is tonically activated by ambient levels of endogenous agonist(s). We further show that EPPTB blocks the TAAR1-mediated activation of an inwardly rectifying K(+) current. When applied alone, EPPTB induces an apparent inward current, suggesting the closure of tonically activated K(+) channels. Importantly, these EPPTB effects were absent in Taar1 knockout mice, ruling out off-target effects. We additionally found that both the acute application of EPPTB and the constitutive genetic lack of TAAR1 increase the potency of DA at D2 receptors in DA neurons. In summary, our data support that TAAR1 tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of DA neurons in the VTA. We hypothesize that the EPPTB-induced increase in the potency of DA at D2 receptors is part of a homeostatic feedback mechanism compensating for the lack of inhibitory TAAR1 tone.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.