ArticlePsychopharmacology2014
Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- A Full-Spectrum Evaluation of Sigma-1 Receptor (S1R) Positron Emission Tomography (PET) Radioligands from Binding Affinity to Clinical Imaging.Molecules (Basel, Switzerland) · 2025Review
- Repurposing Sigma-1 Receptor-Targeting Drugs for Therapeutic Advances in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Effect of Donepezil Hydrochloride in the Twitcher Mouse Model of Krabbe Disease.Molecular neurobiology · 2024Article
- Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.CNS drugs · 2023Review
- Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis.The European journal of neuroscience · 2022Article
- Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands.Biomolecules · 2022Review
- Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis.International journal of molecular sciences · 2021Review
- Multi-Target Directed Ligands (MTDLs) Binding the σInternational journal of molecular sciences · 2021Review
- Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy.Expert opinion on therapeutic targets · 2021Review
- Wildtype σ1 receptor and the receptor agonist improve ALS-associated mutation-induced insolubility and toxicity.The Journal of biological chemistry · 2020Article
- Tactics for preclinical validation of receptor-binding radiotracers.Nuclear medicine and biology · 2017Review
- Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [(11)C]SA4503.Molecular imaging and biology · 2016Article
- Cocaine occupancy of sigma1 receptors and dopamine transporters in mice.Synapse (New York, N.Y.) · 2016Article
- Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses.Psychopharmacology · 2015Article
- Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy.Molecular imaging and biology · 2015Article
- Altered sigma-1 receptor expression in two animal models of cognitive impairment.Molecular imaging and biology · 2015Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleSigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Alzheimer's disease, is also a high-affinity sigma-1 agonist.
objectivesThe objectives of the present study were to investigate if the sigma-1 agonist tracer (11)C-SA4503 and microPET can be used to determine sigma-1 receptor occupancy (RO) of donepezil in the rat brain; to establish RO of donepezil at doses commonly used in rodent behavioural studies; and to determine the effective plasma concentration of donepezil required for 50 % of max-min occupancy (EC50).
methodsMale Wistar rats were pre-treated with donepezil (0.1 to 10 mg/kg) for about 1 h before microPET scans using (11)C-SA4503. The total distribution volume (V T) of the tracer was determined by Logan graphical analysis using time activity curves from arterial plasma and regions of interest drawn around the entire brain and individual brain regions. RO by donepezil was calculated from a modified Lassen plot, and ED50 was estimated from the sigmoidal dose-response curves obtained when the RO was plotted against log donepezil dose.
resultsA dose-dependent reduction was observed for V T in the whole brain as well as individual brain regions. RO increased dose-dependently and was 93 % at 10 mg/kg. ED50 was 1.29 mg/kg.
conclusionsDonepezil, in the common dose range, was found to dose-dependently occupy a significant fraction of the sigma-1 receptor population. The data indicate that it is possible to determine sigma-1 RO by an agonist drug in rat brain, using (11)C-SA4503 and microPET.
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