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

@article{Lindekens2004InVS,
  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},
  year={2004},
  volume={17},
  pages={1408-1413}
}
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… 

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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.

TLDR
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?

TLDR
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.

TLDR
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.