ArticleNeuropharmacology2013
Positive allosteric modulator of α7 nicotinic-acetylcholine receptors, PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates.
Article in Neuropharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 104 citations in OpenAlex.
- Alzheimer's Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective.International journal of molecular sciences · 2025Review
- Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.Brain : a journal of neurology · 2025Review
- The efficacy of an allosteric modulator of the alpha 7 nicotinic acetylcholine receptor in a murine model of stroke.Frontiers in neuroscience · 2025Article
- Modulation of CaScientific reports · 2024Article
- α7 nicotinic acetylcholine receptors are necessary for basal forebrain activation to increase expression of the nerve growth factor receptor TrkA.bioRxiv : the preprint server for biology · 2024Article
- Exposing the latent phenotype of Gulf War Illness: examination of the mechanistic mediators of cognitive dysfunction.Frontiers in immunology · 2024Review
- Dose-Dependent Dissociation of Pro-cognitive Effects of Donepezil on Attention and Cognitive Flexibility in Rhesus Monkeys.Biological psychiatry global open science · 2023Article
- Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer's disease.Heliyon · 2022Review
- Activation of Cholinergic Anti-Inflammatory Pathway Ameliorates Cerebral and Cardiac Dysfunction After Intracerebral Hemorrhage Through Autophagy.Frontiers in immunology · 2022Article
- The Basal Forebrain Cholinergic Nuclei and Their Relevance to Schizophrenia and Other Psychotic Disorders.Frontiers in psychiatry · 2022Review
- A cellular approach to understanding and treating Gulf War Illness.Cellular and molecular life sciences : CMLS · 2021Article
- Effects of nicotinic antagonists on working memory performance in young rhesus monkeys.Neurobiology of learning and memory · 2021Article
- Differential effects of alkaloids on memory in rodents.Scientific reports · 2021Article
- Aged rhesus monkeys: Cognitive performance categorizations and preclinical drug testing.Neuropharmacology · 2021Article
- Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.Pharmacological reports : PR · 2020Article
- The α7 nicotinic acetylcholine receptor positive allosteric modulator prevents lipopolysaccharide-induced allodynia, hyperalgesia and TNF-α in the hippocampus in mice.Pharmacological reports : PR · 2019Article
- Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys.Neuropharmacology · 2019Article
- Facilitation and inhibition of firing activity and N-methyl-D-aspartate-evoked responses of CA1 hippocampal pyramidal cells by alpha7 nicotinic acetylcholine receptor selective compounds in vivo.Scientific reports · 2019Article
- Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model.Acta pharmacologica Sinica · 2019Article
- Nicotine-like discriminative stimulus effects of acetylcholinesterase inhibitors and a muscarinic receptor agonist in Rhesus monkeys.Drug development and industrial pharmacy · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The development of novel therapeutic agents for disorders of cognition such as Alzheimer's disease (AD) is of paramount importance given the ever-increasing elderly population, however; there is also considerable interest in any strategy that might enhance the clinical efficacy of currently available treatments. The purpose of this study was to evaluate an adjunctive treatment strategy to memory enhancement, namely combining the commonly prescribed acetylcholinesterase inhibitor (AChEI) donepezil, with a positive allosteric modulator (PAM) of α7 nicotinic-acetylcholine receptors (α7-nAChRs), PNU-120596. The treatment strategy was evaluated in a (non-spatial) spontaneous novel object recognition (NOR) task in young rats; a water maze spatial learning and recall procedure in aged, cognitively-impaired rats, and a delayed match to sample (working/short term memory) task in aged rhesus monkeys. In all three experiments a similar drug response was observed, namely that donepezil administered alone improved task performance in a dose-dependent manner; that PNU-120596 administered alone was without significant effect, but that the combination of PNU-120596 with a subthreshold dose of donepezil was effective. The positive effect of the drug combination appeared to be α7-nAChR mediated given that it was blocked in the NOR task by the selective α7-nAChR antagonist methyllycaconitine (MLA). Collectively, these data indicate that PNU-120596 increases the effective dose range of donepezil in learning/memory-related tasks in young and age-impaired animal models. The results suggest that α7-nAChR-selective PAMs like PNU-120596 have potential as adjunctive treatments with acetylcholinesterase inhibitors (e.g., donepezil) for age-related illnesses such as AD as well memory disorders not necessarily associated with advanced age.
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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.