1. Nootropic Activity of a Novel (-)-Cytisine Derivative (3aR,4S,8S,12R, 12aS,12bR)-10-Methyl-2-Phenyloctahydro-1H-4,12a-Etheno-8,12-Methanopyrrolo[3',4':3,4]Pyrido[1,2-a] [1,5]Diazocine-1,3,5(4H)-Trione.
- Author
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Makara NS, Sapozhnikova TA, Khisamutdinova RY, Tsypysheva IP, Borisevich SS, Kovalskaya AV, Petrova PR, Khursan CL, and Zarudii FS
- Subjects
- Alkaloids chemical synthesis, Animals, Avoidance Learning drug effects, Azocines chemical synthesis, Azocines pharmacology, Binding Sites, Female, Gene Expression, Male, Mice, Molecular Docking Simulation, Nootropic Agents chemical synthesis, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Quinolizines chemical synthesis, Quinolizines pharmacology, Rats, Rats, Wistar, Receptors, AMPA agonists, Receptors, AMPA antagonists & inhibitors, Receptors, AMPA metabolism, Receptors, Kainic Acid agonists, Receptors, Kainic Acid antagonists & inhibitors, Receptors, Kainic Acid metabolism, Structure-Activity Relationship, Toxicity Tests, Acute, Alkaloids pharmacology, Nootropic Agents pharmacology, Receptors, AMPA chemistry, Receptors, Kainic Acid chemistry
- Abstract
We performed screening of nootropic properties of 10 new derivatives of quinolizidine alkaloid (-)-cytisine. Compounds with β-endo stereochemistry were more active than α-endo-isomers. Under stress conditions (3aR,4S,8S,12R,12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3',4':3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione enhanced memory and had a positive effect on cognitive functions of rats. According to molecular docking data, the nootropic activity of the compound can be associated with its affinity for the glutamate-binding subunits GluK1 and GluR2 of the kainate and AMPA receptor, respectively.
- Published
- 2018
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