In Vivo Study of the Effect of Valpromide and Valnoctamide in the Pilocarpine Rat Model of Focal Epilepsy

  title={In Vivo Study of the Effect of Valpromide and Valnoctamide in the Pilocarpine Rat Model of Focal Epilepsy},
  author={Hilde Lindekens and Ilse Smolders and Ghous M. Khan and Meir Bialer and Guy Ebinger and Yvette Michotte},
  journal={Pharmaceutical Research},
AbstractPurpose. We evaluated the effectiveness of the commonly used antiepileptic drug sodium valproate (400 mg/kg) and two of its amide derivatives, valpromide and valnoctamide (both 100 mg/kg), in an in vivo rat model of focal epilepsy. Our main interest was to get insight into possible changes in extracellular amino acid neurotransmitter levels following administration of the drugs, both in control and in epileptic conditions. Methods. Seizures were evoked in freely moving rats by… 

New insights from the use of pilocarpine and kainate models

Effects of Three Anti-Seizure Drugs on Cholinergic and Metabolic Activity in Experimental Status Epilepticus.

  • I. ImranK. KochHenrik SchöferH. LauJ. Klein
  • Biology, Medicine
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
  • 2019
Hippocampal ACh release closely follows seizure activity in SE and is attenuated when SE subsides, and the effects of three anti-seizure drugs on changes of acetylcholine energy metabolites and oxidative stress during SE are reported.

Amidic modification of valproic acid reduces skeletal teratogenicity in mice.

Findings clearly indicate that VPD and VCD are distinctly less teratogenic than VPA in the induction of not only neural tube defects, but also skeletal abnormalities.

Structure-function studies for the panacea, valproic acid.

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Results revealed previously unknown details of structural reorganization of the septohippocampal cholinergic system in experimental epilepsy, involving fiber sprouting into the dentate molecular layer and a parallel fiber retraction from the Dentate hilus.



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Only certain antiepileptic drugs prevent seizures induced by pilocarpine

Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats.

The observed alterations in extracellular hippocampal amino acid levels support the hypothesis that muscarinic receptor stimulation by the intrahippocampal administration of 10 mM pilocarpine is responsible for the seizure onset, and that the amino acids maintain the sustained seizure activity.

Can we develop improved derivatives of valproic acid?

2-n-propyl-2-pentenoatc and/or a valpromide isomer, which does not undergo amide acid biotransformation and preferably is not an epoxide hydrolase inhibitor, may prove to be improved derivatives of the parent compound valproic acid.

Disposition of valpromide, valproic acid, and valnoctamide in the brain, liver, plasma, and urine of rats.

Monitoring the levels of these two amide isomers in the brain, liver, plasma, and urine of rats found that VCD and VPD distribute better into the brain than VPA, a fact that may contribute to their better anticonvulsant activity.