9913. Valproic Acid

Nomenclature

CAS number: 99-66-1
2-Propylpentanoic acid; 2-propylvaleric acid; di-n-propylacetic acid; Convulex (Pharmacia); Depakene (Abbott).
C8H16O2; mol wt 144.21.
C 66.63%, H 11.18%, O 22.19%.

Description and references

Antiepileptic; increases levels of γ-aminobutyric acid (GABA) in the brain. Prepn: B. S. Burton, Am. Chem. J. 3, 385 (1882); E. Oberreit, Ber. 29, 1998 (1896); M. Tiffeneau, Y. Deux, Compt. Rend. 212, 105 (1941). LC-MS/MS determn in plasma: D. S. Jain et al., Talanta 72, 80 (2007). Anticonvulsant activity: H. Meunier et al., Therapie 18, 435 (1963). Comprehensive description: Z. L. Chang, Anal. Profiles Drug Subs. 8, 529-556 (1979). Review of teratogenicity studies: H. Nau et al., Pharmacol. Toxicol. 69, 310-321 (1991); R. Alsdorf, D. F. Wyszynski, Expert Opin. Drug Saf. 4, 345-353 (2005). Review of pharmacology and clinical experience in epilepsy: E. M. Rimmer, A. Richens, Pharmacotherapy 5, 171-184 (1985); in psychiatric disease: D. R. P. Guay, ibid. 15, 631-647 (1995); in migraine prophylaxis: C. E. Shelton, J. F. Connelly, Ann. Pharmacother. 30, 865-866 (1996). Review of pharmacodynamics and mechanisms of action: W. Lscher, Prog. Neurobiol. 58, 31-59 (1999).

Chemical structure

Properties

Colorless liquid with characteristic odor. bp 219.5°. nD24.5 1.425. d40 0.9215. pKa 4.6. Very sol in organic solvents. Soly in water: 1.3 mg/ml. LD50 orally in rats: 670 mg/kg See: Jenner et al., Food Cosmet. Toxicol. 2, 327 (1964).

Derivative

Sodium salt (1:1).

Nomenclature

CAS number: 1069-66-5
Sodium valproate; Depacon (Abbott); Depakin (Sanofi-Synthelabo); Dépakine (Sanofi-Aventis); Epilim (Sanofi-Aventis); Ergenyl (Sanofi-Synthelabo); Leptilan (Dolorgiet); Orfiril (Desitin).
C8H15NaO2; mol wt 166.19.
C 57.82%, H 9.10%, Na 13.83%, O 19.25%.

Properties

White, odorless, crystalline, deliquescent powder. pKa 4.8. Hygroscopic. One gram is sol in 0.4 ml water; 1.5 ml ethanol; 5 ml methanol. Practically insol in common organic solvents. LD50 orally in mice: 1700 mg/kg (Meunier).

Derivative

Sodium salt (2:1).

Nomenclature

CAS number: 76584-70-8
Sodium hydrogen bis(2-propylpentanoate); divalproex sodium; valproate semisodium; Abbott 50711; Depakote (Abbott); Valcote (Abbott).
C16H31NaO4; mol wt 310.40.
C 61.91%, H 10.07%, Na 7.41%, O 20.62%.

Derivative

Magnesium salt.

Nomenclature

Depamag (Sigma-Tau).
C16H30MgO4; mol wt 310.71.
C 61.85%, H 9.73%, Mg 7.82%, O 20.60%.

Therapeutic Category

Anticonvulsant; antimanic; antimigraine.

Therapeutic Category (Veterinary)

Anticonvulsant.

Keywords

Anticonvulsant; Antimigraine; Antimanic