ArticlePsychopharmacology2013
Pharmacological and behavioral profile of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141), a novel α7 nicotinic acetylcholine receptor agonist/serotonin 5-HT3 receptor antagonist.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 18 citations in OpenAlex.
- ABT-126 monotherapy in mild-to-moderate Alzheimer's dementia: randomized double-blind, placebo and active controlled adaptive trial and open-label extension.Alzheimer's research & therapy · 2016Trial
- Intestinal microbiota improves inflammation and cognitive function in the brain of a7nAChR deficient rat through the gut brain axis.Scientific reports · 2025Article
- α7 nicotinic acetylcholine receptors as therapeutic targets in schizophrenia: Update on animal and clinical studies and strategies for the future.Neuropharmacology · 2020Review
- 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
- Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein.Neurobiology of disease · 2018Article
- Article
- The role of serotonin in memory: interactions with neurotransmitters and downstream signaling.Experimental brain research · 2014Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
RATIONALE AND
objectiveAgonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/serotonin 5-HT3 receptor (5-HT3R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects.
resultsEVP-5141 bound to α7 nAChRs in rat brain membranes (K i = 270 nM) and to recombinant human serotonin 5-HT3Rs (K i = 880 nM) but had low affinity for α4β2 nAChRs (K i > 100 μM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT3R antagonist but did not block α3β4, α4β2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg(-1), p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg(-1)) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg(-1), p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg(-1), i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg(-1), p.o.).
conclusionsEVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that α7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.
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