Disease relevance of trans-2-Ene-valproic acid

• It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity [1].
• The transfer of valproic acid (VPA, 2-propylpentanoic acid) and its unsaturated active metabolite (2-en, 2-propyl-2-pentenoic acid) from plasma to liver has been studied in the mouse between 2 min and 6 h following oral administration of 50 mg of the sodium salts per kg body weight [2].

High impact information on trans-2-Ene-valproic acid

• Whereas the rapid onset of the effect on electroconvulsive threshold and on GABA metabolism can be explained by the rapid entrance of VPA into brain, the carry-over effects observed correlated with the kinetics of the metabolite 2-propyl-2-pentenoic acid better than with those of VPA due to the persistence of this metabolite in brain [3].
• Valproic acid exhibited an anti-proliferative IC50 of 1.45 mM, whereas 2-propyl-2-pentenoic acid and 2-propyl-4-pentenoic acid were virtually indistinguishable, exhibiting significantly lower IC50 values of 2.5 and 2.55 mM, respectively [4].
• Diffusion analysis of valproate and trans-2-en-valproate in agar and in cerebral cortex of the rat [5].
• The effect of phenobarbital on the potential hepatotoxicity of E-2-en-valproate (E-2-en-VPA; trans-2-en-VPA) and VPA was studied in young male Sprague-Dawley rats [6].
• Pharmacokinetics, anticonvulsant efficacy, and adverse effects of trans-2-en-valproate after acute and chronic administration in amygdala-kindled rats [7].

Biological context of trans-2-Ene-valproic acid

• Pharmacokinetics and enterohepatic circulation of (E)-2-ene valproic acid in the rat [8].

Anatomical context of trans-2-Ene-valproic acid

• In this mouse model, valproic acid induced between 20% (400 mg/kg dose) and 60% (600 mg/kg dose) incidence of exencephaly in living fetuses; 2-en-valproic acid was not teratogenic at these dose levels [9].

References