Objectives: The purpose of this study was to investigate the central activity of the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic 5HT1A receptor agonists and postsynaptic 5HT1A , 5HT2A and D2 receptors antagonists. The compounds were examined using animal tests towards antipsychotic, antidepressant- and anxiolytic-like properties and then compared with effects evoked by an atypical antipsychotic drug ziprasidone.
Methods: D-amphetamine-induced hyperactivity test was used to determine antipsychotic-like activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test were conducted to investigate antidepressant- and antianxiety-like activity, respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone were administered intraperitoneally 60 min before the tests. Diazepam and imipramine were used as standard anxiolytic and antidepressant drugs, respectively.
Key findings: The obtained results demonstrate that new synthesized compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties in behavioural tests in mice.
Conclusions: The present preclinical results indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine-2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an antipsychotic drug with additional antidepressant and anxiolytic properties.
Keywords: antidepressant-like activity; axiolytic-like activity; imidazo[2,1-f]theophylline; ziprasidone.
© 2014 Royal Pharmaceutical Society.