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

ABSTRACT

Introduction

The discovery of the anticonvulsant properties of valproic acid and the development 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.

KEYWORDS:

• Valproic acid
• valproate
• divalproex
• drug development
• history

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This manuscript was supported by the Ministry of Education of the Republic of Serbia under grant [no. 175007].