Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid , found naturally in valerian .  Valproic acid is a carboxylic acid , a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol -induced convulsions in laboratory rats .  It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.  Valproic acid has also been used for migraine prophylaxis and bipolar disorder. 
Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans . Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug. As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all members of the azole family.  
The neurotoxin MPTP had been known earlier to cause PD-like symptoms (in humans and other primates, though not in rats) by interfering with complex I in the electron transport chain and killing dopaminergic neurons in the substantia nigra. However, further studies involving MPTP have failed to show development of Lewy bodies , a key component to PD pathology. Therefore, the mechanism behind MPTP as it relates to Parkinson's disease is not fully understood.  Because of these developments, rotenone was investigated as a possible Parkinson-causing agent. Both MPTP and rotenone are lipophilic and can cross the blood–brain barrier .