Valproate

Since the fortuitous discovery of its anticonvulsant activIty in 1962, valproate has established itself worldwide as a major antiepileptic drug against several types of epileptic seizures. Clinical experience with valpro­ ate has continued to grow in recent years, including use of valproate for diseases other than epilepsy, for example in bipolar disorders and migraine. In this volume on valproate emphasis is placed on the scientific back­ ground leading to the discovery of val pro ate, its subsequent pharmacologi­ cal and toxicological characterization, and its clinical development into one of the most widely and successfully used anti epileptic drugs, a real mile­ stone in drug therapy. The current state of knowledge of valproate will be reviewed by experts in the field, including new hypotheses about its mecha­ nisms of action, its metabolism into pharmacologically active metabolites, its unique distribution characteristics, its unwanted hepatotoxic and terato­ genic adverse effects and its various clinical uses. Furthermore, the wide variety of available pharmaceutical formulations of valproate, including novel controlled-release formulations, will be outlined. The monograph is aimed at a broad readership, particularly neurologists, psychiatrists and basic scientists working in the field of epilepsy research. Because the monograph also deals with structure-activity relationships of valproate as well as of its metabolites and analogs, the book should also serve for rese­ archers working in medicinal chemistry, particularly in the pharmaceutical industry.

The discovery of valproate.- The pharmacology of valproate.- Pharmacological effects and mechanisms of action.- Chemistry and biotransformation.- Absorption, distribution and excretion.- Toxicity.- Clinical use of valproate.- Valproate in the treatment of epilepsies in children.- Treatment of epilepsies in adults.- Valproate use in psychiatry: A focus on bipolar illness.- Valproate in the treatment of headache.- Adverse effects and interactions with other drugs.- The future of valproate.