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Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats
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SYSNO ASEP 0542146 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats Author(s) Mareš, Pavel (FGU-C) RID, ORCID
Tsenov, Grygoriy (FGU-C) RID, ORCID
Kubová, Hana (FGU-C) RID, ORCIDArticle number 415 Source Title Pharmaceutics. - : MDPI
Roč. 13, č. 3 (2021)Number of pages 15 s. Language eng - English Country CH - Switzerland Keywords NMDA receptors ; GluN2A subunit ; anticonvulsant action ; pentylenetetrazol-induced seizures ; cortical epileptic afterdischarges ; immature rats Subject RIV FR - Pharmacology ; Medidal Chemistry OECD category Pharmacology and pharmacy R&D Projects GA19-11931S GA ČR - Czech Science Foundation (CSF) GA18-09296S GA ČR - Czech Science Foundation (CSF) EF16_025/0007444 GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000634070000001 EID SCOPUS 85103080287 DOI 10.3390/pharmaceutics13030415 Annotation The GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors becomes dominant during postnatal development, overgrowing the originally dominant GluN2B subunit. The aim of our study was to show changes of anticonvulsant action of the GluN2A subunit-preferring antagonist during postnatal development of rats. Possible anticonvulsant action of GluN2A-preferring antagonist of NMDA receptors P = [[[(1S)-1-(4-bromophenyl)ethyl]amino](1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]phosphonic acid tetrasodium salt (PEAQX) (5, 10, 20 mg/kg s.c.) was tested in 12-, 18-, and 25-day-old rats in three models of convulsive seizures. Pentylenetetrazol-induced generalized seizures with a loss of righting reflexes generated in the brainstem were suppressed in all three age groups in a dose-dependent manner. Minimal clonic seizures with preserved righting ability exhibited only moderately prolonged latency after the highest dose of PEAQX. Anticonvulsant action of all three doses of PEAQX against cortical epileptic afterdischarges (generated in the forebrain) was found in the 25-day-old animals. The highest dose (20 mg/kg) was efficient also in the two younger groups, which might be due to lower specificity of PEAQX and its partial affinity to the GluN2B subunit. Our results are in agreement with the postero-anterior maturation gradient of subunit composition of NMDA receptors (i.e., an increase of GluN2A representation). In spite of the lower selectivity of PEAQX, our data demonstrate, for the first time, developmental differences in comparison with an antagonist of NMDA receptors with a dominant GluN2B subunit. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://www.mdpi.com/1999-4923/13/3/415
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