Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A 2A receptors in mice.

Autor: Dziubina A; Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland. Electronic address: anna.dziubina@uj.edu.pl., Szmyd K; Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Zygmunt M; Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Sapa J; Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Dudek M; Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Filipek B; Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Drabczyńska A; Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland., Załuski M; Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland., Pytka K; Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland., Kieć-Kononowicz K; Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2016 Dec; Vol. 68 (6), pp. 1285-1292. Date of Electronic Publication: 2016 Jul 25.
DOI: 10.1016/j.pharep.2016.07.008
Abstrakt: Background: It has recently been suggested that the adenosine A 2A receptor plays a role in several animal models of depression. Additionally, A 2A antagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants.
Methods: In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A 2A receptors but poor A 1 affinity were evaluated for their antidepressant- and anxiolytic-like activity. The activity of these derivatives was tested using a tail suspension and forced swim test, two widely-used behavioral paradigms for the evaluation of antidepressant-like activity. In turn, the anxiolytic activity was evaluated using the four-plate test.
Results: The results showed the antidepressant-like activity of pyrimido- and imidazopurinedione derivatives (i.e. KD 66, KD 167 and KD 206) in acute and chronic behavioral tests in mice. KD 66 revealed an anxiolytic-like effect, while KD 167 increased anxiety behaviors. KD 206 had no effect on anxiety. Furthermore, none of the tested compounds increased locomotor activity.
Conclusion: Available data support the proposition that the examined compounds with adenosine A 2A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents.
(Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)
Databáze: MEDLINE
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