Valproic Acid

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Cat Number

API0231552

CAS Number

99-66-1

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CAS Number

99-66-1

EINECS

202-777-3

Storage

Store at room temperature

Synonyms

2-Propylvaleric acid; Dipropylacetic acid; Depakene; Depakine; Mylproin

Molecular Formula

C8H16O2

Molecular Weight

144.21

Smiles

CCCC(CCC)C(=O)O

Appearance

Clear colorless to pale yellow liquied

Melting Point

-21.25℃

Boiling Point

220℃

General Description

Valproic acid is a branched-chain fatty acid with broad-spectrum anticonvulsant and mood-stabilizing properties, available in multiple formulations including delayed-release capsules, extended-release tablets, and as an intravenous solution. It is also used as divalproex sodium, a coordination complex that is better tolerated due to reduced gastrointestinal irritation. This agent remains a first-line treatment for several seizure types and bipolar disorder.

Mechanism of Action

Valproic acid exerts its effects through multiple mechanisms, including enhancement of gamma-aminobutyric acid (GABA) synthesis and inhibition of GABA transaminase, leading to increased brain GABA concentrations. It also blocks voltage-gated sodium channels, reduces T-type calcium currents, and modulates the inositol signaling pathway. These combined actions stabilize neuronal membranes, reduce seizure propagation, and dampen manic episodes, though the precise antimanic mechanism is not fully understood.

Application

It is indicated as monotherapy or adjunctive therapy for complex partial seizures, absence seizures, and generalized tonic-clonic seizures, as well as for prophylaxis of migraine headaches. It is also approved for the treatment of acute manic and mixed episodes associated with bipolar disorder. Valproate carries significant teratogenic risk, including neural tube defects and reduced IQ in exposed offspring, and is contraindicated during pregnancy unless no alternative exists. Monitoring of liver function, platelet count, and serum drug levels is essential.

In a rat spinal cord injury (SCI) model, valproic acid (VPA) treatment shifted microglial polarization from pro‑inflammatory M1 to anti‑inflammatory M2, reduced inflammatory cytokines (TNF‑α, IL‑1β, IL‑6, IFN‑γ), and improved functional recovery. Mechanistically, VPA inhibited HDAC3 nuclear translocation and activity, enhancing acetylation of STAT1 and NF‑κB p65. Increased acetylation of NF‑κB p65 and its complex formation with STAT1 suppressed NF‑κB transcriptional activity, attenuating microglia‑mediated central inflammation. The authors conclude that VPA exerts neuroprotective effects after SCI by modulating microglial phenotype through STAT1‑mediated acetylation of the NF‑κB pathway in an HDAC3‑dependent manner.

Fig. 1 VPA protects neurons against SCI-induced neuronal apoptosis in the lesioned spinal cord 7 days after SCI. (Chen S, et al., 2018)

References

Chen S, et al. Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3. J Neuroinflammation. 2018; 15(1):150.

RNA‑sequencing of hepatocytes under hyperglycemic conditions revealed activation of complement and coagulation cascade genes. Treatment with the histone deacetylase inhibitor valproic acid (VPA) reversed this activation. Many of these gene expression changes coincided with alterations in histone acetylation at their promoters, indicating an epigenetic mechanism. This study provides a molecular basis for VPA’s potential to mitigate hyperglycemia‑driven hepatic inflammation and thrombosis risk.

Fig. 2 Effect of VPA stimulation on hyperglycaemic HepG2 gene expression. (Felisbino MB, et al., 2021)

References

Felisbino MB, et al. Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways. Sci Rep. 2021; 11(1):2163.

Does Valproic Acid require protection from light during long-term storage?

Yes, it is photosensitive. Exposure to light can cause discoloration and degradation. Store in light-resistant, tightly sealed containers, preferably amber glass.

What is the recommended storage temperature for Valproic Acid?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, as it is a liquid at room temperature (freezing point ~ -15°C) and can oxidize faster at higher temperatures.

Is Valproic Acid sensitive to oxidation, and how is this prevented?

Yes, it is prone to oxidative degradation. Our packaging includes nitrogen purging to create an inert atmosphere, and we recommend storage in original containers.

How is the impurity 2-propylpent-4-enoic acid (ene-valproic acid) monitored?

This key degradation product is specifically quantified using a validated GC or HPLC method, ensuring it remains below ICH limits throughout shelf life.