The Neuroactive Steroid Pregnanolone Glutamate: Anticonvulsant Effect, Metabolites and Its Effect on Neurosteroid Levels in Developing Rat Brains
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023761%3A_____%2F22%3AN0000009" target="_blank" >RIV/00023761:_____/22:N0000009 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/22:00551648 RIV/67985823:_____/22:00551648 RIV/00023752:_____/22:43920803
Result on the web
<a href="https://www.mdpi.com/1424-8247/15/1/49" target="_blank" >https://www.mdpi.com/1424-8247/15/1/49</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ph15010049" target="_blank" >10.3390/ph15010049</a>
Alternative languages
Result language
angličtina
Original language name
The Neuroactive Steroid Pregnanolone Glutamate: Anticonvulsant Effect, Metabolites and Its Effect on Neurosteroid Levels in Developing Rat Brains
Original language description
Pregnanolone glutamate (PA-G) is a neuroactive steroid that has been previously demonstrated to be a potent neuroprotective compound in several biological models in vivo. Our in vitro experiments identified PA-G as an inhibitor of N-methyl-D-aspartate receptors and a potentiator of gamma-aminobutyric acid receptors (GABA(A)Rs). In this study, we addressed the hypothesis that combined GABA(A)R potentiation and NMDAR antagonism could afford a potent anticonvulsant effect. Our results demonstrated the strong age-related anticonvulsive effect of PA-G in a model of pentylenetetrazol-induced seizures. PA-G significantly decreased seizure severity in 12-day-old animals, but only after the highest dose in 25-day-old animals. Interestingly, the anticonvulsant effect of PA-G differed both qualitatively and quantitatively from that of zuranolone, an investigational neurosteroid acting as a potent positive allosteric modulator of GABA(A)Rs. Next, we identified 17-hydroxy-pregnanolone (17-OH-PA) as a major metabolite of PA-G in 12-day-old animals. Finally, the administration of PA-G demonstrated direct modulation of unexpected neurosteroid levels, namely pregnenolone and dehydroepiandrosterone sulfate. These results suggest that compound PA-G might be a pro-drug of 17-OH-PA, a neurosteroid with a promising neuroprotective effect with an unknown mechanism of action that may represent an attractive target for studying perinatal neural diseases.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmaceuticals
ISSN
1424-8247
e-ISSN
1424-8247
Volume of the periodical
15
Issue of the periodical within the volume
1
Country of publishing house
CH - SWITZERLAND
Number of pages
19
Pages from-to
Article Number 49
UT code for WoS article
000757087600001
EID of the result in the Scopus database
2-s2.0-85122128797