Evaluation of anticonvulsant activity of novel pyrrolidin-2-one derivatives

Jacek Sapa; Małgorzata Zygmunt; Katarzyna Kulig; Barbara Malawska; Magdalena Dudek; Barbara Filipek; Marek Bednarski; Aleksandra Kusak; Gabriel Nowak

doi:10.1016/j.pharep.2014.02.014

Evaluation of anticonvulsant activity of novel pyrrolidin-2-one derivatives

Pharmacol Rep. 2014 Aug;66(4):708-11. doi: 10.1016/j.pharep.2014.02.014. Epub 2014 Mar 6.

Authors

Jacek Sapa¹, Małgorzata Zygmunt², Katarzyna Kulig³, Barbara Malawska³, Magdalena Dudek⁴, Barbara Filipek⁴, Marek Bednarski², Aleksandra Kusak², Gabriel Nowak⁵

Affiliations

¹ Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland. Electronic address: jaceksapa@interia.pl.
² Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
³ Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Krakow, Poland.
⁴ Chair of Pharmacodynamics, Jagiellonian University, Medical College, Krakow, Poland.
⁵ 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.

PMID: 24948076
DOI: 10.1016/j.pharep.2014.02.014

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.

Conclusion: 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.

Keywords: Anticonvulsant activity; Epilepsy; Pyrrolidin-2-one derivatives.

MeSH terms

Animals
Anticonvulsants / administration & dosage
Anticonvulsants / chemistry
Anticonvulsants / pharmacology
Anticonvulsants / therapeutic use*
Behavior, Animal / drug effects
Disease Models, Animal
Electroshock
Ligands
Male
Mice
Pentylenetetrazole / pharmacology
Pyrrolidinones / administration & dosage
Pyrrolidinones / chemistry
Pyrrolidinones / pharmacology
Pyrrolidinones / therapeutic use*
Receptor, Serotonin, 5-HT1A / metabolism
Receptors, Adrenergic, alpha-1 / metabolism
Seizures / chemically induced
Seizures / drug therapy*
Seizures / etiology
Seizures / metabolism

Substances

Anticonvulsants
Ligands
Pyrrolidinones
Receptors, Adrenergic, alpha-1
Receptor, Serotonin, 5-HT1A
Pentylenetetrazole