Epileptic disorders need treatment for many years or even for life, and this makes a thorough understanding of the pharmacokinetics and possible hazards and side effects of the drugs used in treatment mandatory. During recent decades our knowledge in this field has considerably increased, not least as a result of the development of specific and sensitive methods for the determination of anti­ epileptic agents in biological material. The clinical pharmacology of this group of drugs has been studied extensively and can today be regarded as well established. This does not necessarily mean that drug treatment of epilepsy is without problems. For example, it has recently been shown that one of the newer anti­ epileptic drugs, greeted with great enthusiasm by clinicians, may in rare instances induce serious damage to the liver and the pancreas, and seems even to have a certain teratogenic potential. Clinical problems should be understood as a challenge to the experimental pharmacologist, who should try to find explanations for the clinical hazards, and, if possible, show new ways in which better drugs might be developed. In recent years interest has focused on the importance of the inhibitory transmitter 'l'-aminobutyric acid (GABA) in the pathophysiology of epilepsy, and there have been a series of attempts to find useful antiepileptic drugs among substances interfering with GABA metabolism in the CNS.

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Clinical Aspects of Epileptic Diseases.- 1 Epilepsy: Seizures and Syndromes.- A. Definition.- B. Epidemiology.- C. Classification.- D. Epileptic Seizures.- E. Syndromes of Epilepsy.- F. Age-Related Syndromes.- I. Neonatal Convulsions (Neonatal Seizures).- II. Febrile Convulsions.- III. Epilepsy with Infantile Spasms (West Syndrome, Infantile Spasms, Epilepsy with Propulsive Petit Mai).- IV. Epilepsy with Myoclonic-Astatic Seizures (Lennox-Gastaut Syndrome.- V. Epilepsy with Frequent Absences (Friedmann Syndrome, Pyknolepsy).- VI. Epilepsy with Juvenile Myoclonic Jerks (Herpin-Janz Syndrome, Epilepsy with Impulsive Petit Mai, Juvenile Myoclonic Epilepsy).- VII. Awakening Epilepsy (Epilepsy with Nonfocal Grand Mai).- VIII. Benign Focal Epilepsy of Childhood [Benign Epilepsy of Children with Rolandic (Centrotemporal) Foci].- G. Age-Unrelated Epilepsy Syndromes.- I. Epilepsies with Complex Focal (Psychomotor) Seizures (Temporal, Rhinencephalic, Limbic Epilepsy).- II. Epilepsies with Simple Focal Seizures (Neocortical Epilepsy, Epilepsy with Jacksonian Seizures, Adversive Seizures, Sensory Auras, Sensory Seizures).- III. Status Epilepticus.- IV. Syndromes of Seizures Elicited by Sensory Stimuli (So-called Reflex Epilepsies).- References.- 2 Electroencephalography.- A. Introduction.- B. Main Forms of Epileptiform Patterns.- C. Focal Epileptiform Activity.- D. Bilateral Epileptiform Patterns.- E. Activation Procedures.- F. Electrocorticography and Depth-recording.- References.- 3 Epilepsy in Animals.- A. Introduction.- B. Acquired Epilepsies in Animals.- C. Inherited Epilepsies in Animals.- I. Photomyoclonic Seizures in the Baboon (Papio papio).- II. Inherited Epilepsy in Dogs.- III. Inherited Epilepsy in Mongolian Gerbils (Meriones unguiculatus).- IV. Inherited Epilepsy in Domestic Fowl.- D. Concluding Remarks.- References.- Pathophysiology of Seizure Disorders.- 4 Intermediary Metabolism.- A. Introduction.- B. Brain Energy Reserves and the Cell Redox Potential.- I. Cerebral Energy Use During Seizures.- II. Brain Redox Potential and Lactic Acidosis.- C. Seizures and Glycolytic Flux.- I. Regulation of Glycolysis: Phosphofructokinase.- II. Hexokinase.- III. Pyruvate Kinase.- D. The Citric Acid Cycle and Epileptic Seizures.- I. Energy Metabolism.- II. Amino Acid Metabolism.- III. Ammonia Metabolism.- E. Free Fatty Acid Metabolism.- F. Metabolic Mechanisms of Neuronal-Cell Damage During Status Epilepticus.- I. Role of Extracerebral Factors.- II. Role of Sustained Cell Firing.- III. Role of Energy Failure.- IV. Lactic Acidosis.- V. Calcium "Cytotoxicity".- G. Epileptic Seizures in the Neonate.- I. Mobilization of Glycogen Reserves.- II. Limited Transport Capacity of the Blood-brain Barrier.- References.- 5 Monoamines and the Pathophysiology of Seizure Disorders.- A. Introduction.- B. Catecholamines.- I. Electrically Induced Seizures.- II. Seizures Induced by Chemical Agents.- III. Reflex Epilepsy Models.- IV. Other Models of Epilepsy.- C. Serotonin.- I. Electrically Induced Seizures.- II. Seizures Induced by Pentylenetetrazol.- III. Reflex Epilepsy Models.- D. Histamine.- E. Conclusions.- References.- 6 Acetylcholine.- A. Introduction.- B. Effect of Cholinergic Drugs on Susceptibility to Seizures.- C. Effect of Experimental and Spontaneous Seizures on the Cholinergic System.- I. Electroshock and Convulsant Drugs.- II. Spontaneous and Audiogenic Convulsions.- III. Focal Epilepsy.- D. Kindling and the Cholinergic System.- E. Conclusions.- References.- 7 GABA and Other Amino Acids.- A. Introduction: Amino Acids as Neurotransmitters.- B. Amino Acids Producing Inhibition.- I. Introduction.- II. GABA.- III. Glycine.- IV. Taurine.- C. Amino Acids Producing Excitation.- I. Dicarboxylic Amino Acids.- II. Sulphinic and Sulphonic Acids.- D. Concluding Remarks.- I. Inherited Abnormalities of Amino Acid Metabolism and Epilepsy.- II. Amino Acids and Antiepileptic Drugs.- References.- 8 Prostaglandins.- A. Introduction.- B. Effects of Prostaglandins on Experimentally Induced Convulsions.- C. Convulsant Effect of Prostaglandins.- D. Release of Prostaglandins During Convulsions.- E. Conclusions.- References.- General Pharmacology of Antiepileptic Drugs.- 9 Chemical Constitution and Pharmacological Effect.- A. Introduction.- B. Five-Membered Heterocyclic Compounds.- I. Hydantoins.- II. Oxazolidinediones.- III. Succinimides.- C. Six-Membered Heterocyclic Compounds.- I. Barbiturates and Other Compounds.- II. Phenobarbital and Primidone.- D. Acyl Ureas.- E. Tricyclic Compounds: Carbamazepine.- F. Benzodiazepines.- G. Valproic Acid.- H. Miscellaneous Compounds.- References.- 10 Biochemistry.- A. Introduction.- B. Ionic Permeability.- I. Effects on Sodium Conductance.- II. Effects on Calcium Conductance.- III. Effects on Potassium Conductance.- IV. Effects on Chloride Conductance.- C. Neurotransmitter Metabolism, Disposition, and Dynamics.- I. Effects on Intracellular Processes Related to Transmitter Release.- II. Effects on Neurotransmitter Metabolism and Disposition.- III. Effects on Receptor-Ionophore Dynamics.- D. Perspective.- References.- 11 Tolerance and Dependence.- A. Introduction.- B. Tolerance.- I. Metabolic Tolerance.- II. Functional Tolerance.- III. Acute Tolerance.- IV. Conclusions.- C. Physical Dependence.- I. Experimental Evidence.- II. Clinical Evidence.- III. Conclusions.- References.- 12 Animal Experimental Methods in the Study of Antiepileptic Drugs.- A. Introduction.- B. Models of Epileptiform Phenomena in Animals.- I. Electrically Induced Seizures.- II. Chemically Induced Ictal and Interictal States (Exclusive of Metals).- III. Focal Epileptogenesis Through Local Application of Metals or Metal Salts.- IV. Local Freezing as Epileptogenic Factor.- V. Models for Secondary and Progressive Epileptogenic Lesions.- VI. Animals with "Inborn" Epilepsy: Genetic Models.- VII. Circadian Aspects.- C. Some Nonsymptomatic Models.- I. Biophysical Approach.- II. Biochemical Approach.- D. Discussion.- I. Models for Screening.- II. Testing for "Special Indications".- References.- Appendix to Chapter 12 Antiepileptic Drug Development Program.- A. Antiepileptic Drug Development Programm.- B. Anticonvulsant Screening Project.- I. Phase I.- II. Phase II.- III. Phase III.- IV. Phase IV.- V. Phase V.- VI. Phase VI.- VII. Phase VII.- C. Toxicity/Selected Pharmacology Project.- D. Primate Model of Epilepsy.- E. Controlled Clinical Trials.- References.- Specific Pharmacology of Antiepileptic Drugs.- 13 Hydantoins.- A. Introduction.- B. Chemistry.- I. Physicochemical Prope…