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

• Published in: Bulletin of experimental biology and medicine Vol. 164; no. 4; pp. 434 - 438
• Main Authors: Makara, N. S., Sapozhnikova, T. A., Khisamutdinova, R. Yu, Tsypysheva, I. P., Borisevich, S. S., Kovalskaya, A. V., Petrova, P. R., Khursan, C L., Zarudii, F. S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2018; Springer Nature B.V
• Subjects: Alkaloids - chemical synthesis; Alkaloids - pharmacology; Animals; Avoidance Learning - drug effects; Azocines - chemical synthesis; Azocines - pharmacology; Binding Sites; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cognitive ability; Cognitive enhancement; Female; Gene Expression; Glutamic acid receptors; Internal Medicine; Isomers; Laboratory Medicine; Male; Memory; Mice; Molecular Docking Simulation; Nootropic Agents - chemical synthesis; Nootropic Agents - pharmacology; Pathology; Pharmacology and Toxicology; 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 - chemistry; Receptors, AMPA - metabolism; Receptors, Kainic Acid - agonists; Receptors, Kainic Acid - antagonists & inhibitors; Receptors, Kainic Acid - chemistry; Receptors, Kainic Acid - metabolism; Stereochemistry; Structure-Activity Relationship; Toxicity Tests, Acute; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; nootropic activity; molecular docking; (-)-cytisine; mnestic activity
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-018-4006-0

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 (3a
R
,4
S
,8
S
,12
R
,12a
S
,12b
R
)-10-methyl-2-phenyloctahydro-1
H
-4,12a-etheno-8,12-methanopyrrolo[3’,4’:3,4]pyrido[1,2-
a
] [1,5]diazocine-1,3,5(4
H
)-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.