ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
AT-1001: a high affinity and selective α3β4 nicotinic acetylcholine receptor antagonist blocks nicotine self-administration in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 76 citations in OpenAlex.
- An accessory orthosteric ligand binding site in the (α3)Cell reports · 2026Article
- Hippocampal Metabolomics Reveal the Mechanism of α-Conotoxin [S9K]TxID Attenuating Nicotine Addiction.Marine drugs · 2026Article
- Evaluation of (S)-T1 and (S)-T2 ligands targeting α3β4 nAChR as potential nicotine addiction pharmacotherapy.Psychopharmacology · 2024Article
- Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions.International journal of molecular sciences · 2023Review
- Elucidating the reinforcing effects of nicotine: a tribute to Nadia Chaudhri.Psychopharmacology · 2023Review
- What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.Journal of medicinal chemistry · 2023Review
- (-)-Adaline from theMolecules (Basel, Switzerland) · 2022Article
- Nicotinic Acetylcholine Receptor Partial Antagonist Polyamides from Tunicates and Their Predatory Sea Slugs.ACS chemical neuroscience · 2021Article
- Tobacco smoke exposure enhances reward sensitivity in male and female rats.Psychopharmacology · 2021Article
- α3* Nicotinic Acetylcholine Receptors in the Habenula-Interpeduncular Nucleus Circuit Regulate Nicotine Intake.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity.Frontiers in immunology · 2021Review
- α-Conotoxin TxID and [S9K]TxID, α3β4 nAChR Antagonists, Attenuate Expression and Reinstatement of Nicotine-Induced Conditioned Place Preference in Mice.Marine drugs · 2020Article
- Article
- Differences in mechanisms underlying reinstatement of cigarette smoke extract- and nicotine-seeking behavior in rats.Neuropharmacology · 2020Article
- Neuronal nicotinic acetylcholine receptors mediate ∆Addiction biology · 2020Article
- Article
- A behavioral economic analysis of the value-enhancing effects of nicotine and varenicline and the role of nicotinic acetylcholine receptors in male and female rats.Behavioural pharmacology · 2018Article
- Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys.The Journal of pharmacology and experimental therapeutics · 2018Article
- Differential regulation of alcohol taking and seeking by antagonism at α4β2 and α3β4 nAChRs.Psychopharmacology · 2018Article
- Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula.The international journal of biochemistry & cell biology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Genomic and pharmacologic data have suggested the involvement of the α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) in drug seeking to nicotine and other drugs of abuse. In order to better examine this receptor subtype, we have identified and characterized the first high affinity and selective α3β4 nAChR antagonist, AT-1001, both in vitro and in vivo. This is the first reported compound with a Ki below 10 nM at α3β4 nAChR and >90-fold selectivity over the other major subtypes, the α4β2 and α7 nAChR. AT-1001 competes with epibatidine, allowing for [³H]epibatidine binding to be used for structure-activity studies, however, both receptor binding and ligand-induced Ca²⁺ flux are not strictly competitive because increasing ligand concentration produces an apparent decrease in receptor number and maximal Ca²⁺ fluorescence. AT-1001 also potently and reversibly blocks epibatidine-induced inward currents in HEK cells transfected with α3β4 nAChR. Importantly, AT-1001 potently and dose-dependently blocks nicotine self-administration in rats, without affecting food responding. When tested in a nucleus accumbens (NAcs) synaptosomal preparation, AT-1001 inhibits nicotine-induced [³H]dopamine release poorly and at significantly higher concentrations compared with mecamylamine and conotoxin MII. These results suggest that its inhibition of nicotine self-administration in rats is not directly due to a decrease in dopamine release from the NAc, and most likely involves an indirect pathway requiring α3β4 nAChR. In conclusion, our studies provide further evidence for the involvement of α3β4 nAChR in nicotine self-administration. These findings suggest the utility of this receptor as a target for smoking cessation medications, and highlight the potential of AT-1001 and congeners as clinically useful compounds.
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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.