Not all significant drug discoveries arise from the application of theoretical principles, complex experimental designs and analyses, or years of animal and human testing. Valproic acid, a highly significant drug for the management of seizures and mood disorders, was discovered quite by chance.
During the course of doctoral research at the University of Lyon in France, graduate student Pierre Eymard needed a solvent for his newly synthesized chemicals in order to evaluate their potential antiepileptic effects. He selected valproic acid, which was synthesized in 1881. Rather unexpectedly, the compounds tested all had similar antiseizure effects in animals, thanks to the seemingly inactive solvent. Clinical trials were initiated in 1964, and the drug was approved for marketing as an antiepileptic drug in France in 1967, in the United Kingdom and other European countries in 1974, and in the United States in 1978.
Unlike other antiseizure drugs, valproic acid is effective against a wide range of seizure types in both children and adults. Although it works in ways that are not yet determined, because it causes minimal sedation and few serious side effects, it is often the first drug selected for these conditions. But its choice as a “go-to” drug does not suggest that the administration of valproic acid (Depakene, among other trade names) is without danger. In rare instances, its use has been associated with fatal liver toxicity—a risk that is greatly magnified in children under the age of two.
Valproic acid also effectively controls manic excitement in bipolar disorders and is used as a mood stabilizer to prevent recurring episodes of mania and depression. Additionally, it has been approved for the prevention of migraine headaches. Early studies published in 2010 suggest that valproic acid may be effective for the treatment of retinitis pigmentosa, a severe neurodegenerative disease of the retina that ultimately results in blindness.
SEE ALSO Phenobarbital (1912), Dilantin (1938), Lithium (1949).
Jacques-Louis David created this oil painting, Napoleon Crossing the Alps (1800). Many medical experts believe Napoleon had psychogenic attacks brought on by stress and epileptic seizures due to chronic uremia associated with gonorrhea.