7-3-Chlorophenypiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione as a serotonin receptor ligands with potential antidepressant activity

Background the previous study showed that arylpiperazine can condition affinity to α-adrenoceptors,5-ht1a/5-ht2a receptors and compounds with arylpiperazine had antidepressant-like effect. the aim of this study was to determine the antidepressant-like activity of new arylpiperazines containing novel 8-alkoxy-purine-2,6-dione fragments. methods new 3-chloroarylpiperazinylalkyl analogs of 8-alkoxy-purine-2,6-dione and their purine-2,6,8-trione analogs (2-5) were tested for their α1,α2,5-ht1a,5-ht2a,and 5-ht7 receptor affinities in radioreceptor binding study. moreover,in search for potential antidepressant properties of these compounds,the forced swim test in mice was conducted. results compounds 2 and 3 were potent 5-ht1a receptor ligands with ki within the range on 12-15 nm. all investigated compounds were found to be highly active 5-ht2a receptor (ki 15-28 nm) and α1 adrenoceptor (ki 21-89 nm) ligands. in the forced swim test all the compounds showed a significantly activity in spite of their reducing ability of locomotor activity. the most potent effect was produced by compound 4 and 5,which reduced the immobility time in this test in all used doses. conclusion in our study the most potent antidepressant-like activity was produced by compounds 4 and 5,which are selective for the 5-ht2a and α1 receptors. © 2014 institute of pharmacology,polish academy of sciences. all rights reserved.