title: Antidepressant-like activity of the phenylpiperazine pyrrolidin-2-one derivatives in mice.
abstract: 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-HT2 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.
authors: Department of Pharmacodynamic, Laboratory of Pharmacological Screening, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland. jaceksapa@interia.pl
authors: Jacek
authors: J
authors: Sapa
authors: Barbara
authors: B
authors: Filipek
authors: Katarzyna
authors: K
authors: Kulig
authors: Barbara
authors: B
authors: Malawska
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011760:Pyrrolidinones / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D013550:Swimming
chemical_list: D000889:Anti-Arrhythmia Agents; D000928:Antidepressive Agents; D000959:Antihypertensive Agents; D010879:Piperazines; D011760:Pyrrolidinones; D044348:Receptors, Serotonin, 5-HT2; D044282:Receptor, Serotonin, 5-HT1A; C031503:phenylpiperazine