{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:12:16Z","timestamp":1773267136279,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>A series of 22 new<jats:italic>N<\/jats:italic>\u2010[(4\u2010phenylpiperazin\u20101\u2010yl)\u2010methyl]\u20103\u2010methyl\u2010pyrrolidine\u20102,5\u2010dione and pyrrolidine\u20102,5\u2010dione derivatives were synthesized and evaluated for their anticonvulsant activities in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (<jats:italic>sc<\/jats:italic>PTZ) seizure tests after intraperitoneal injection into mice. The neurotoxicity was determined applying the rotarod test. The<jats:italic>in vivo<\/jats:italic>results in mice showed that seven compounds were effective in the MES or\/and<jats:italic>sc<\/jats:italic>PTZ seizure tests. The quantitative evaluation in both tests after i.p. administration into mice revealed that the most active compounds were<jats:italic>N<\/jats:italic>\u2010[{4\u2010(3,4\u2010dichlorophenyl)\u2010piperazin\u20101\u2010yl}\u2010methyl]\u20103\u2010methylpyrrolidine\u20102,5\u2010dione (<jats:bold>12<\/jats:bold>) with ED<jats:sub>50<\/jats:sub>\u2009=\u200916.13\u2009mg\/kg (MES), ED<jats:sub>50<\/jats:sub>\u2009=\u2009133.99\u2009mg\/kg (<jats:italic>sc<\/jats:italic>PTZ) and<jats:italic>N<\/jats:italic>\u2010[{4\u2010(3,4\u2010dichlorophenyl)\u2010piperazin\u20101\u2010yl}\u2010methyl]\u2010pyrrolidine\u20102,5\u2010dione (<jats:bold>23<\/jats:bold>) with ED<jats:sub>50<\/jats:sub>\u2009=\u200937.79\u2009mg\/kg (MES), ED<jats:sub>50<\/jats:sub>\u2009=\u2009128.82\u2009mg\/kg (<jats:italic>sc<\/jats:italic>PTZ), whereas<jats:italic>N<\/jats:italic>\u2010[{4\u2010(3\u2010trifluoromethylphenyl)\u2010piperazin\u20101\u2010yl}\u2010methyl]\u2010pyrrolidine\u20102,5\u2010dione (<jats:bold>24<\/jats:bold>) was effective only in the MES test with ED<jats:sub>50<\/jats:sub>\u2009=\u200916.37\u2009mg\/kg. These molecules showed higher potency and also lower neurotoxicity than the reference antiepileptic drugs such as ethosuximide and valproic acid.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201400152","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T11:28:59Z","timestamp":1408447739000},"page":"768-776","source":"Crossref","is-referenced-by-count":20,"title":["Synthesis, Physicochemical, and Anticonvulsant Properties of New<i>N<\/i>\u2010Mannich Bases Derived from Pyrrolidine\u20102,5\u2010dione and Its 3\u2010Methyl Analog"],"prefix":"10.1002","volume":"347","author":[{"given":"Sabina","family":"Rybka","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Medicinal Chemistry Jagiellonian University, Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Obniska","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Medicinal Chemistry Jagiellonian University, Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Rapacz","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacodynamics Jagiellonian University, Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Filipek","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacodynamics Jagiellonian University, Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Medicinal Chemistry Jagiellonian University, Medical College Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,19]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"583","volume-title":"The Phamacological Basis of Therapeutics","author":"McNamara J. 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