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The discovery of valproate

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Part of the Milestones in Drug Therapy book series (MDT)


Like many important discoveries in the history of pharmacology, valproate was not developed by any “rational strategy,” but its anticonvulsant activity was serendipitously discovered by Pierre Eymard in France in 1962. Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton [1], but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by Eymard. Because valproic acid is a liquid, it was used as a lipophilic vehicle to dissolve water-insoluble compounds during preclinical drug testing. As part of his thesis in 1962, Eymard had synthesized a number of khelline derivatives in the laboratory of G. Carraz at the School of Medicine and Pharmacy in Grenoble, France [2]. Two colleagues, H. Meunier and Y. Meunier, working for a small company, Berthier Laboratories, in Grenoble, had used valproate for a long time as a vehicle for dissolving of a bismuth salt. So the three scientists Eymard, Meunier and Meunier had the idea to use this vehicle also for dissolving some of the khelline derivatives synthesized by Eymard. In order to evaluate the pharmacological activities of the khelline derivatives, Carraz proposed to test the most active derivative in the pentylenetetrazole (PTZ) seizure test. By doing this, the researchers found that the vehicle, valproate, alone exerted an anticonvulsant effect.


  • Valproic Acid
  • Anticonvulsant Activity
  • Anticonvulsant Effect
  • Active Derivative
  • Audiogenic Seizure

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© 1999 Springer Basel AG

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Löscher, W. (1999). The discovery of valproate. In: Löscher, W. (eds) Valproate. Milestones in Drug Therapy. Birkhäuser, Basel.

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