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Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2A receptors in mice

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Abstract

Background

It has recently been suggested that the adenosine A2A receptor plays a role in several animal models of depression. Additionally, A2A 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 A2A receptors but poor A1 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 A2A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents.

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Authors and Affiliations

  1. Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland

    Anna Dziubina, Karina Szmyd, Magdalena Dudek, Barbara Filipek & Karolina Pytka

  2. Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland

    Małgorzata Zygmunt & Jacek Sapa

  3. Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland

    Anna Drabczyńska, Michał Załuski & Katarzyna Kieć-Kononowicz

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  1. Anna Dziubina
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  2. Karina Szmyd
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  3. Małgorzata Zygmunt
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  4. Jacek Sapa
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Correspondence to Anna Dziubina.

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Dziubina, A., Szmyd, K., Zygmunt, M. et al. Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2A receptors in mice. Pharmacol. Rep 68, 1285–1292 (2016). https://doi.org/10.1016/j.pharep.2016.07.008

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  • DOI: https://doi.org/10.1016/j.pharep.2016.07.008

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