Wave-Like Dose-Dependence of the Stimulating Effects of Dimebon on Cognition in a Wide Dose Range
Comparison of the cognition-stimulating effects of Dimebon in a wide dose range revealed a non-monotonic and nontrivial wave-like dose-dependence of its activity. Positive results were obtained at low (0.02-0.05 mg/kg) or high (5-10 mg/kg) doses of Dimebon, while intermediate doses were ineffective. This type of the dose dependence of the pharmacological effect can indicate that the substance has several targets. This fact should be taken into consideration when selecting the doses and concentrations of the substance and its analogues for further studies, and for planning treatment schemes and administration doses in clinical studies.
Key wordscognition-stimulating effect Dimebon dose dependence multitarget effects
Unable to display preview. Download preview PDF.
- 4.Bharadwaj PR, Bates KA, Porter T, Teimouri E, Perry G, Steele JW, Gandy S, Groth D, Martins RN, Verdile G. Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases. Transl. Psychiatry. 2013;3. ID e332. doi: 10.1038/tp.2013.97CrossRefGoogle Scholar
- 7.Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, Hung D; Dimebon investigators. Effect of Dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebocontrolled study. Lancet. 2008;372:207-215.Google Scholar
- 9.Makhaeva GF, Sokolov VB, Shevtsova EF, Kovaleva NV, Lushchekina SV, Boltneva NP, Rudakova EV, Aksinenko AY, Shevtsov PN, Neganova ME, Dubova LG, Bachurin SO. Focused design of polypharmacophoric neuroprotective compounds: conjugates of γ-carbolines with carbazole derivatives and tetrahydrocarbazole. Pure Appl. Chem. 2017;89(8):1167-1184.CrossRefGoogle Scholar
- 13.Strekalova T, Bahzenova N, Trofimov A, Schmitt-Böhrer AG, Markova N, Grigoriev V, Zamoyski V, Serkova T, Redkozubova O, Vinogradova D, Umriukhin A, Fisenko V, Lillesaar C, Shevtsova E, Sokolov V, Aksinenko A, Lesch KP, Bachurin S. Pro-neurogenic, memory-enhancing and anti-stress effects of DF302, a novel fluorine gamma-carboline derivative with multi-target mechanism of action. Mol. Neurobiol. 2018;55(1):335-349.CrossRefGoogle Scholar