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

Abstract

Available data support the proposition that the examined compounds with adenosine A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents.

Safety issues of compounds acting on adenosinergic signalling

“…Much more promising results have been observed in clinical trials of A 2A AdR antagonists for treating neurodegenerative diseases such as PD and for immunotherapy of cancers. A recent report also evaluates antidepressant‐like and anxiolytic‐like activity in mice of purinedione derivatives with A 2A AdR antagonistic activity . A 3 AdR agonists are being investigated in clinical trial setting for the treatment of autoimmune disorders (CF101) and for the treatment of hepatocellular carcinoma (CF102).…”

“…A recent report also evaluates antidepressant-like and anxiolytic-like activity in mice of purinedione derivatives with A 2A AdR antagonistic activity. [134] A 3 AdR agonists are being investigated in clinical trial setting for the treatment of autoimmune disorders (CF101) and for the treatment of hepatocellular carcinoma (CF102). CF102 was well tolerated among patients and showed increased survival rate.…”

The influence of selective A1 and A2A receptor antagonists on the antidepressant-like activity of moclobemide, venlafaxine and bupropion in mice

“…Moreover, it is widely known that the behavioural despair tests used in our experiments are differently sensitivity to various agents, particularly those that affect the serotonergic neurotransmission [for review see ]. Although the TST is regarded as a useful tool detecting an antidepressant‐like potential of a wide range of compounds: starting from typical antidepressant drugs, going through the atypical ones, and ending with new agents, like antagonists of adenosine receptors, some other ‘not typical’ agents (such as rolipram and levoprotiline) are not active in this test. In turn, the selective serotonin reuptake inhibitors are not consistently responsive to the FST .…”

“…Moreover, several authors state that the compounds with adenosine A 2A receptor affinity may provide an interesting option for the development of antidepressant agents with rapid onset of activity. [18,19] In our previous in-vivo studies, we showed that caffeine, a non-selective inhibitor of the adenosine receptors, not only exerted by itself an antidepressant-like activity in the FST and the TST in mice when given acutely, but also potentiated the effect of antidepressant drugs belonging to different pharmacological groups. [20][21][22] It is generally known that caffeine antagonizes all four adenosine receptor subtypes and also acts as a phosphodiesterase inhibitor; therefore, the observed results could have been a resultant of this multiway antidepressant mechanism of action.…”

“…found out that mice lacking the adenosine A 2A receptors were significantly more active in the FST and the TST as compared to their counterparts from the wild‐type control. Moreover, several authors state that the compounds with adenosine A 2A receptor affinity may provide an interesting option for the development of antidepressant agents with rapid onset of activity …”