ArticleBiochemical pharmacology2009
TC-5619: an alpha7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia.
Article in Biochemical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
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Who cites it
53 citing papers in PubMed, 138 citations in OpenAlex.
- Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia.Schizophrenia bulletin · 2016Trial
- AQW051, a novel, potent and selective α7 nicotinic ACh receptor partial agonist: pharmacological characterization and phase I evaluation.British journal of pharmacology · 2015Trial
- A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- The effects of pharmacologic estradiol on anxiety-related behavior in adolescent and adult female mice.Physiology & behavior · 2025Article
- Acetylcholine receptor based chemogenetics engineered for neuronal inhibition and seizure control assessed in mice.Nature communications · 2024Article
- Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig.Frontiers in neuroimaging · 2024Article
- The potential role of nicotine in breast cancer initiation, development, angiogenesis, invasion, metastasis, and resistance to therapy.Breast cancer (Tokyo, Japan) · 2022Review
- Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics.Translational psychiatry · 2022Review
- Evidence for AlphaThe Journal of pharmacology and experimental therapeutics · 2022Article
- α7 nicotinic acetylcholine receptors as therapeutic targets in schizophrenia: Update on animal and clinical studies and strategies for the future.Neuropharmacology · 2020Review
- Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies.Neuropharmacology · 2020Review
- In Vitro and In Vivo Characterization of Dibenzothiophene Derivatives [Molecules (Basel, Switzerland) · 2020Article
- Using Xenopus oocytes in neurological disease drug discovery.Expert opinion on drug discovery · 2020Review
- Synthesis, Pharmacological Characterization, and Structure-Activity Relationships of Noncanonical Selective Agonists for α7 nAChRs.Journal of medicinal chemistry · 2019Article
- Nicotinic Acetylcholine Receptor Ligands, Cognitive Function, and Preclinical Approaches to Drug Discovery.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Review
- Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Review
- Overcoming the Limitations of γ- and δ-C-H Arylation of Amines through Ligand Development.Journal of the American Chemical Society · 2018Article
- Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation.European journal of medicinal chemistry · 2018Article
- The current agonists and positive allosteric modulators ofActa pharmaceutica Sinica. B · 2017Review
- Effects of haloperidol, olanzapine, ziprasidone, and PHA-543613 on spatial learning and memory in the Morris water maze test in naïve and MK-801-treated mice.Brain and behavior · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A growing body of evidence suggests that the alpha7 neuronal nicotinic receptor (NNR) subtype is an important target for the development of novel therapies to treat schizophrenia, offering the possibility to address not only the positive but also the cognitive and negative symptoms associated with the disease. In order to probe the relationship of alpha7 function to relevant behavioral correlates we employed TC-5619, a novel selective agonist for the alpha7 NNR subtype. TC-5619 binds with very high affinity to the alpha7 subtype and is a potent full agonist. TC-5619 has little or no activity at other nicotinic receptors, including the alpha4beta2, ganglionic (alpha3beta4) and muscle subtypes. The transgenic th(tk-)/th(tk-) mouse model that reflects many of the developmental, anatomical, and multi-transmitter biochemical aspects of schizophrenia was used to assess the antipsychotic effects of TC-5619. In these mice TC-5619 acted both alone and synergistically with the antipsychotic clozapine to correct impaired pre-pulse inhibition (PPI) and social behavior which model positive and negative symptoms, respectively. Antipsychotic and cognitive effects of TC-5619 were also assessed in rats. Similar to the results in the transgenic mice, TC-5619 significantly reversed apomorphine-induced PPI deficits. In a novel object recognition paradigm in rats TC-5619 demonstrated long-lasting enhancement of memory over a wide dose range. These results suggest that alpha7-selective agonists such as TC-5619, either alone or in combination with antipsychotics, could offer a new approach to treating the constellation of symptoms associated with schizophrenia, including cognitive dysfunction.
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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.