2-(propyl-1,1-d2)-pentanoic-3,3-d2acid,monosodiumsalt

Description

Valproic acid-d₄ (sodium salt) is intended for use as an internal standard for the quantification of valproic acid by GC- or LC-MS. Valproic acid is an analog of the natural fatty acid valeric acid that inhibits class I histone deacetylases (HDACs) with an IC₅₀ value of approximately 2 mM.¹ It decreases the number of axon branches in sensory neurons isolated from newborn rat dorsal root ganglia, an effect that is reversed by inositol-1,4,5-trisphosphate (1,4,5-IP₃).² In vivo, valproic acid inhibits amyloid-β deposition and neuritic plaque formation and decreases escape latency in the Morris water maze, indicating improved memory performance, in the APP23 transgenic mouse model of Alzheimer's disease.³ Valproic acid has anticonvulsant activity in the pentylenetetrazol seizure threshold test in mice (ED₅₀ = 0.71 mmol/kg) but induces neurotoxicity when administered at doses greater than or equal to 1.2 mmol/kg.⁴ Formulations containing valproic acid have been used to treat bipolar disorder and various seizure disorders.

References

1. G?ttlicher, M., Minucci, S., Zhu, P., et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells EMBO J. 20(24),6969-6978(2001).
2. Williams, R.S.B., Cheng, L., Mudge, A.W., et al. A common mechanism of action for three mood-stabilizing drugs Nature 417(6886),292-295(2002).
3. Qing, H., He, G., Ly, P.T., et al. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer’s disease mouse models J. Exp. Med. 205(12),2781-2789(2008).
4. Elmazar, M.M., Hauck, R.S., and Nau, H. Anticonvulsant and neurotoxic activities of twelve analogues of valproic acid J. Pharm. Sci. 82(12),1255-1258(1993).