Lessons learned from the discovery of sodium valproate and what has this meant to future drug discovery efforts?

Abstract

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. Introduction: The discovery of of the anticonvulsant properties of valproic acid and the development of of valproic acid/valproate to market authorization for specific epilepsy types and syndromes, as well as their repurposing for other indications, are illustrative examples of both the strengths and weaknesses of drug development strategies. Areas covered: This review summarizes and interprets the development and repurposing history of valproic acid/valproate. The article is based on articles, including original studies and systematic reviews obtained from PubMed, Scopus, Ebsco, Scindeks and Google Scholar databases. Expert opinion: Random screening and careful observation of the experimental effects of tested substances were crucial for discovering the anticonvulsant effects of valproic acid, while rational drug design and clinical observation strategies led to repurposing valproic acid and valproate for bipolar disorder maintenance treatmentand prevention of migraine attacks. Early planning and feasibility studies of future clinical trials are essential for obtaining marketing authorization of new substances or new indications of old anticonvulsants. Significant progress has been made recently toward understanding, treatment and prevention of hepatotoxicity caused by valproic acid/valproate, making its long-term administration safer. There are ongoing efforts to repurpose valproic acid/valproate for augmentation with antipsychotic drugs for the treatment of schizophrenia.