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."

Over 12 million people with epilepsy have seizures that cannot be controlled by antiepileptic drugs. The term "drug-resistance" is abundantly used in the epilepsy literature but the definitions proposed differ considerably. It is used indifferently in a number of different settings: as a criterion for selection of patients eligible for new antiepileptic drug trials, for the selection of surgical candidates, for the design of epidemiological studies, for the design of studies on quality of life, for the definition of the epileptic encephalopathies (in comparison to more benign epilepsy syndromes), to mention but a few. As a result, available studies are usually not comparable and referral to epilepsy specialists is unacceptably delayed. The volume includes several focused chapters on all issues relating to drug-resistance and offers the basis for a consensus on a clinically meaningful core definition.