Synthesis of new piperazine derivatives and investigation of their antidepressant-like effects

In this study, the structures of newly synthesized piperazine derivatives were elucidated by various spectroscopic methods. The antidepressant-like activities of the derivatives were evaluated with modified forced swimming and tail suspension tests while their effects on the motor performance of animals were assessed with the activitymeter test. Compounds 3a, 3d, 3f, and 3i decreased the immobility periods of the animals in the tail suspension and modified forced swimming tests. These derivatives increased the duration of climbing and swimming behaviors of animals in the modified forced swimming test. These data point out that compounds 3a, 3d, 3f and 3i exhibit antidepressant-like activity. In the activitymeter test, the compounds did not cause any changes in the ambulatory activity values, total activity counts, or walking distances of the mice. These results indicate that the antidepressant-like effects of compounds 3a, 3d, 3f and 3i are specific. Studies were conducted with p-chlorophenylalanine methyl ester and α-methyl-para-tyrosine methyl ester to investigate the involvement of monoaminergic mechanisms in the antidepressant-like activities of these derivatives. Pretreatment with these agents abolished the anti-immobility activities of compounds 3a, 3d, 3f and 3i. These findings indicate that the antidepressant-like activities of compounds 3a, 3d, 3f, and 3i are mediated by the serotonergic and catecholaminergic systems.