Antidepressant-like activity of the phenylpiperazine pyrrolidin-2-one derivatives in mice

The present study was designed to investigate the central nervous system activity of 23 novel phenylpiperazine pyrrolidin-2-one derivatives. these compounds had marked antiarrhythmic and hypotensive activities and revealed affinity for α1- and α2-adrenoceptors. these effects may be related to their α-adrenolytic properties. we assessed their antidepressant-like effect in the forced swimming test,influence of spontaneous locomotor activities and binding to 5-ht1a and 5-ht 2 receptors. our study demonstrated the strong antidepressant-like activity of compound ep-65 in the forced swimming test. the effect of ep-65 was stronger than results obtained with the classical antidepressants imipramine and mianserin. other compounds,ep-41,ep-42,ep-44,ep-47,ep-48,ep-49,ep-50,ep-62,ep-66,ep-70,ep-75 and ep-76,showed significantly weaker activities in this test. compound ep-42 showed the strongest affinity for 5-ht1a (ki = 24.5 nm),and compound ep-50 showed the strongest affinity for the 5-ht2 receptor (ki = 109.1 nm). all tested compounds significantly suppressed the spontaneous locomotor activity of mice. currently,it is not possible to determine which mechanisms are involved in the witnessed antidepressant-like activity of novel phenylpiperazine pyrrolidin-2-one derivatives. copyright © 2011 by institute of pharmacology polish academy of sciences.