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

Abstract

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 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 A_2A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents.

Keywords: Adenosine A(2A) receptor; Antidepressant activity; Imidazo[2,1-f]purinediones; Pyrimido[2,1-f]purinediones.