title: Evaluation of anticonvulsant activity of novel pyrrolidin-2-one derivatives.
abstract: BACKGROUND
  The aim of this study was to examine the anticonvulsant activity of some novel pyrrolidin-2-one derivatives with considerable affinity to serotonin 5-HT1A and α1-adrenergic receptors.
  
  
  METHODS
  The maximal electroshock-induced seizure (MES) and pentetrazole (PTZ)-induced seizure models in mice were performed.
  
  
  RESULTS
  As a results of the conducted studies, three compounds showing anticonvulsant activity were selected. The EP-40 molecule significantly reduced incidence of seizures in the maximal electroshock test. The EP-42 and EP-46 compounds demonstrated activity in the pentetrazole-induced seizures.
  
  
  CONCLUSIONS
  The results may indicate that the decrease in the susceptibility to seizures induced by the new pyrrolidin-2-one derivatives is related to the significant affinity to serotonergic or α1-adrenergic receptors. Also putative mechanism of action of the test compounds can be linked with their GABA-ergic activity, because these novel derivatives are GABA analogs.
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland. Electronic address: jaceksapa@interia.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kulig
authors.affiliation: Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
authors.affiliation: Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kusak
authors.affiliation: Chair of Pharmacobiology, Jagiellonian University, Medical College, Krakow, Poland; Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences and Center of Excellence in Neuropsychopharmacology, Krakow, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004597:Electroshock; D008024:Ligands; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D008024:Ligands; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D044282:Receptor, Serotonin, 5-HT1A; D010433:Pentylenetetrazole
keywords: Anticonvulsant activity; Epilepsy; Pyrrolidin-2-one derivatives