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--- content:valproate [2020/02/17 11:08] – [History] icna
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 ==== History ====
-Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton[(:cite:burton1882>Burton BS (1882) On the propyl derivatives and decomposition products of ethylacetoacetate. Am Chem J3: 385–395)].Its anticonvulsant activity was fortuitously discovered by Pierre Eymard in France in 1962. 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[(:cite:13935231>{{pubmed>short:13935231}})]. 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[(:cite:loscher1999>Löscher W. (1999) The discovery of valproate. In: Löscher W. (eds) Valproate. Milestones in Drug Therapy. Birkhäuser, Basel)].
+Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton[(:cite:burton1882>Burton BS (1882) On the propyl derivatives and decomposition products of ethylacetoacetate. Am Chem J3: 385–395)].Its anticonvulsant activity was fortuitously discovered by Pierre Eymard in France in 1962 while working at the Firma Berthier laboratories in Grenoble. 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[(:cite:13935231>{{pubmed>short:13935231}})].
+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[(:cite:loscher1999>Löscher W. (1999) The discovery of valproate. In: Löscher W. (eds) Valproate. Milestones in Drug Therapy. Birkhäuser, Basel)].
+It was first released as antiepileptic drug in France in 1967 after the publication of preclinical studies by Carraz et al. in 1964[(:cite:carraz1964>Carraz G, Fau R, Chateau R, Bonnin J (1964) Communication à propos des premiers essais cliniques sur l’activité anti-épileptique de l’acide n-dipropylacétiques (sel de Na). Ann Med Psychol (Paris) 122: 577–585)]. During 1970, it received license to other European countries, but in the USA it was not licensed before 1978.
 ==== References ====
 ~~REFNOTES~~
 Source: Panayiotopoulos CP. (2005). The Epilepsies: Seizures, Syndromes and Management. Oxfordshire (UK): Bladon Medical Publishing.