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C-11, a New Antiepileptic Drug Candidate : Evaluation of the Physicochemical Properties and Impact on the Protective Action of Selected Antiepileptic Drugs in the Mouse Maximal Electroshock-Induced Seizure Model
antiepileptic drugs
maximal electroshock-induced seizures
pharmacokinetic/pharmacodynamic interaction
neuroprotection
physicochemical descriptors
C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various antiepileptic drugs (i.e., carbamazepine CBZ, lacosamide LCM, lamotrigine LTG, and valproate VPA) against maximal electroshock-induced seizures (MES) in mice, as well as its neuroprotective and physicochemical/pharmacokinetic properties. Results indicate that C-11 (30 mg/kg, i.p.) significantly enhanced the anticonvulsant action of LCM (p < 0.001) and VPA (p < 0.05) but not that of CBZ and LTG in the MES test. Neither C-11 (30 mg/kg) alone nor its combination with other anticonvulsant drugs (at their ED50 values from the MES test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength and passive avoidance tests, respectively. Pharmacokinetic characterization revealed that C-11 had no impact on total brain concentrations of LCM or VPA in mice. Qualitative analysis of neuroprotective properties of C-11, after a single administration of pilocarpine, revealed no protective effect of this substance in the tested animals. Determination of physicochemical descriptors showed that C-11 meets the drug-likeness requirements resulting from Lipinski and Veber’s rules and prediction of gastrointestinal absorption and brain penetration, which is extremely important for the CNS-active compounds.
dc.abstract.en | C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various antiepileptic drugs (i.e., carbamazepine CBZ, lacosamide LCM, lamotrigine LTG, and valproate VPA) against maximal electroshock-induced seizures (MES) in mice, as well as its neuroprotective and physicochemical/pharmacokinetic properties. Results indicate that C-11 (30 mg/kg, i.p.) significantly enhanced the anticonvulsant action of LCM (p < 0.001) and VPA (p < 0.05) but not that of CBZ and LTG in the MES test. Neither C-11 (30 mg/kg) alone nor its combination with other anticonvulsant drugs (at their ED50 values from the MES test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength and passive avoidance tests, respectively. Pharmacokinetic characterization revealed that C-11 had no impact on total brain concentrations of LCM or VPA in mice. Qualitative analysis of neuroprotective properties of C-11, after a single administration of pilocarpine, revealed no protective effect of this substance in the tested animals. Determination of physicochemical descriptors showed that C-11 meets the drug-likeness requirements resulting from Lipinski and Veber’s rules and prediction of gastrointestinal absorption and brain penetration, which is extremely important for the CNS-active compounds. | |
dc.affiliation | Wydział Farmaceutyczny : Zakład Chemii Leków | pl |
dc.cm.date | 2021-07-16 | |
dc.cm.id | 104817 | |
dc.cm.idOmega | UJCMa60b0f3e618043a6acdd96934861cf39 | pl |
dc.contributor.author | Zagaja, Mirosław | pl |
dc.contributor.author | Szewczyk, Aleksandra | pl |
dc.contributor.author | Szala-Rycaj, Joanna | pl |
dc.contributor.author | Raszewski, Grzegorz | pl |
dc.contributor.author | Chrościńska-Krawczyk, Magdalena | pl |
dc.contributor.author | Abram, Michał - 178828 | pl |
dc.contributor.author | Kamiński, Krzysztof - 129989 | pl |
dc.contributor.author | Andres-Mach, Marta | pl |
dc.date.accession | 2021-06-29 | pl |
dc.date.accessioned | 2021-07-16T10:17:25Z | |
dc.date.available | 2021-07-16T10:17:25Z | |
dc.date.issued | 2021 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.number | 11 | pl |
dc.description.points | 100 | |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 26 | pl |
dc.identifier.articleid | 3144 | pl |
dc.identifier.doi | 10.3390/molecules26113144 | pl |
dc.identifier.eissn | 1420-3049 | pl |
dc.identifier.issn | 1420-3049 | pl |
dc.identifier.project | ROD UJ / O | pl |
dc.identifier.uri | https://ruj.uj.edu.pl/xmlui/handle/item/276307 | |
dc.identifier.weblink | https://www.mdpi.com/1420-3049/26/11/3144 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.pbn.affiliation | Dziedzina nauk medycznych i nauk o zdrowiu : nauki farmaceutyczne | |
dc.relation.uri | * | |
dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | |
dc.rights.licence | CC-BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | |
dc.share.type | Otwarte czasopismo | |
dc.subject.en | antiepileptic drugs | |
dc.subject.en | maximal electroshock-induced seizures | |
dc.subject.en | pharmacokinetic/pharmacodynamic interaction | |
dc.subject.en | neuroprotection | |
dc.subject.en | physicochemical descriptors | |
dc.subtype | Article | pl |
dc.title | C-11, a New Antiepileptic Drug Candidate : Evaluation of the Physicochemical Properties and Impact on the Protective Action of Selected Antiepileptic Drugs in the Mouse Maximal Electroshock-Induced Seizure Model | pl |
dc.title.journal | Molecules | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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