Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile
| Autor: | José Marco-Contelles, Isabel Iriepa, Eduarda Behenck Medeiros, Josiane Budni, Winnie Deuther-Conrad, Oscar M. Bautista-Aguilera, Francisco López-Muñoz, Francielle Mina, Jose-Manuel Entrena, Ignacio Moraleda |
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| Přispěvatelé: | Universidad Camilo José Cela, European Commission, Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Indoles Monoamine Oxidase Inhibitors medicine.drug_class Monoamine oxidase Histamine Antagonists Pharmacology 03 medical and health sciences Mice 0302 clinical medicine Piperidines In vivo Alzheimer Disease Drug Discovery medicine Animals Cholinesterases Receptors sigma Receptor Donepezil Protein Structure Quaternary Monoamine Oxidase Cognitive deficit Cholinesterase Spatial Memory Amyloid beta-Peptides biology Chemistry Peptide Fragments 030104 developmental biology Monoamine neurotransmitter biology.protein Molecular Medicine Receptors Histamine medicine.symptom Protein Multimerization 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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 Aβ in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil. J.M.-C. thanks MINECO (Grant SAF2015-65586-R), UCJC (Grants 2015-12, 2014-35, and 2015-21), and EU (COST Action CA15135) for support. J.M.-C. thanks Prof. Stark and Prof. Ramsay, as well as Prof. Jia (Beijing Normal University), Dr. Chioua (CSIC), and Dr. Romero (UCM) for their help and support. |
| Databáze: | OpenAIRE |
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