Abstract
Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecular modeling. In addition, contilisant significantly restores the cognitive deficit induced by Aβ1-42 in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / enzymology
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / chemistry
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Animals
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Cholinesterases / metabolism*
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Histamine Antagonists / pharmacology*
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Histamine Antagonists / therapeutic use
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Indoles / pharmacology*
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Indoles / therapeutic use
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Mice
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Monoamine Oxidase / metabolism*
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Monoamine Oxidase Inhibitors / pharmacology*
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Monoamine Oxidase Inhibitors / therapeutic use
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Peptide Fragments / chemistry
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Piperidines / pharmacology*
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Piperidines / therapeutic use
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Protein Multimerization / drug effects
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Protein Structure, Quaternary
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Receptors, Histamine / metabolism*
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Receptors, sigma / agonists*
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Sigma-1 Receptor
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Spatial Memory / drug effects
Substances
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Amyloid beta-Peptides
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Histamine Antagonists
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Indoles
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Monoamine Oxidase Inhibitors
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N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine
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Peptide Fragments
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Piperidines
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Receptors, Histamine
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Receptors, sigma
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amyloid beta-protein (1-42)
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Monoamine Oxidase
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Cholinesterases