Differential toxic and antiepileptic features of Vigabatrin raceme and its enantiomers.
Brain Res
; 1838: 148991, 2024 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-38754803
ABSTRACT
BACKGROUND:
The study aimed to investigate the potential pharmacological and toxicological differences between Vigabatrin (VGB) and its enantiomers S-VGB and R-VGB. The researchers focused on the toxic effects and antiepileptic activity of these compounds in a rat model.METHODS:
The epileptic rat model was established by intraperitoneal injection of kainic acid, and the antiepileptic activity of VGB, S-VGB, and VGB was observed, focusing on the improvements in seizure latency, seizure frequency and sensory, motor, learning and memory deficits in epileptic rats, as well as the hippocampal expression of key molecular associated with synaptic plasticity and the Wnt/ß-catenin/GSK 3ß signaling pathway. The acute toxic test was carried out and the LD50 was calculated, and tretinal damages in epileptic rats were also evaluated.RESULT:
The results showed that S-VGB exhibited stronger antiepileptic and neuroprotective effects with lower toxicity compared to VGB raceme. These findings suggest that S-VGB and VGB may modulate neuronal damage, glial cell activation, and synaptic plasticity related to epilepsy through the Wnt/ß-catenin/GSK 3ß signaling pathway. The study provides valuable insights into the potential differential effects of VGB enantiomers, highlighting the potential of S-VGB as an antiepileptic drug with reduced side effects.CONCLUSION:
S-VGB has the highest antiepileptic effect and lowest toxicity compared to VGB and R-VGB.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vigabatrina
/
Epilepsia
/
Via de Sinalização Wnt
/
Anticonvulsivantes
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article