Cited by 139Pharmacological Receptor Mechanisms and EffectsAlzheimer's disease research and treatmentsCholinesterase and Neurodegenerative Diseases

Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (σ 1 ) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative

Villard, Vanessa, Espallergues, Julie, Keller, Emeline, Vamvakides, Alexandre, Maurice, Tangui·2011·Journal of Psychopharmacology

Abstract

Tetrahydro-N, N-dimethyl-2, 2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) binds to muscarinic acetylcholine and sigma(1) (σ(1)) receptors with affinities in the low micromolar range. We characterized its anti-amnesic and neuroprotective potentials in pharmacological and pathological amnesia models. Spatial working memory was evaluated using spontaneous alternation in the Y-maze and non-spatial memory using passive avoidance procedures. ANAVEX2-73 (0.01-3.0 mg/kg i.p.) alleviated the scopolamine- and dizocilpine-induced learning impairments. ANAVEX2-73 (300 µg/kg) also reversed the learning deficits in mice injected with Aβ(25-35) peptide, a non-transgenic Alzheimer's disease model. When the drug was injected simultaneously with Aβ(25-35), 7 days before the tests, it blocked the appearance of learning impairments. This protective activity was confirmed since ANAVEX2-73 blocked the Aβ(25-35)-induced oxidative stress in the hippocampus. This effect was differentially sensitive to the muscarinic receptor antagonist scopolamine or the σ(1) protein antagonist BD1047, confirming the mixed muscarinic/σ(1) pharmacological action. Finally, its unique demethyl metabolite, ANAVEX19-144, was also effective and ANAVEX2-73 presented a longer duration of action, effective 12 h before Aβ(25-35), than its related compound ANAVEX1-41. The neuroprotective activity of ANAVEX2-73, its mixed cholinergic/σ(1) activity, its low active dose range and its long duration of action together reinforce its therapeutic potential in Alzheimer's disease.

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Crossref · 10.1177/0269881110379286

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  • In preclinical studies, ANAVEX 2-73 showed significant results reverting cognitive impairment in AD mice models, suggesting anti-amnesic and neuroprotective action.

    “In preclinical studies, ANAVEX 2-73 showed significant results reverting cognitive impairment in AD mice models, suggesting anti-amnesic and neuroprotective action [118].”

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Authors
Villard, V., Espallergues, J., Keller, E., Vamvakides, A., & Maurice, T.
Affiliations
  • Inserm (FR)
  • Anavex Life Sciences Corp. (United States) (US)
Venue
Journal of Psychopharmacology
Published
2010-09-09
Volume
25
Issue
8
Pages
1101-1117
ISSN
  • 0269-8811 (ISSN-L)
  • 1461-7285
OpenAlex
W2143538247
Cited by
139
References
60
Citations by year
2026: 9 · 2025: 8 · 2024: 9 · 2023: 15 · 2022: 9 · 2021: 13 · 2020: 13 · 2019: 13 · 2018: 5 · 2017: 11 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 3 · 2012: 5
FWCI
1.56
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
muscarinic receptors, sigma-1 receptor, anti-amnesic effect, neuroprotection, Alzheimer's disease, amyloid beta 25-35, scopolamine-induced amnesia, spatial working memory, passive avoidance memory, oxidative stress, hippocampus, BD1047
MeSH terms
Alzheimer Disease, Animals, Avoidance Learning, Delayed-Action Preparations, Disease Models, Animal, Dose-Response Relationship, Drug, Furans, Hippocampus, Ligands, Male, Memory, Short-Term, Peptide Fragments, Protein Binding, Receptors, Muscarinic, Amyloid beta-Peptides, Receptors, sigma, Oxidative Stress, Neuroprotective Agents, Mice

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