repeated episodes of focal electrical stimulation)probably provide a better screen for predicting efficacy in complex partial seizures. Existing antiseizure drugs provide adequate seizure control in about two thirds of patients.A fraction of the epileptic population is resistant to all available drugs,and this may be due to increased expression of the multidrug transporter P-glycoprotein 170,a product of the ABCBI gene.In children,some severe seizure syndromes associated with progressive brain damage are very difficult to treat.In adults,some focal seizures are refractory to medications.Some,particularly in the temporal lobe, are amenable to surgical resection.Some of the drug-resistant population may respond to vagus-nerve stimulation(VNS),a nonpharmacologic treatment for epilepsy now widely approved for treatment of patients with partial seizures.VNS is indicated for refractory cases or for patients in whom antiseizure drugs are poorly tolerated. Stimulating electrodes are implanted in the left vagus nerve,and the pacemaker is implanted in the chest wall or axilla.Use of this device may permit seizure control with lower doses of drugs. New antiseizure drugs are being sought not only by the screening tests noted above but also by more rational approaches.Compounds are sought that act by one of three mechanisms:(1)enhancement of GABAergic (inhibitory)transmission,(2) diminution of excitatory (usually glutamatergic)transmission,or (3)modification of ionic conductances. I.BASIC PHARMACOLOGY OF ANTISEIZURE DRUGS Chemistry Until 1990,approximately 16 antiseizure drugs were available,and 13 of them can be classified into five very similar chemical groups:barbiturates,hydantoins, oxazolidinediones,succinimides,and acetylureas.These groups have in common a similar heterocyclic ring structure with a variety of substituents(Figure 24-1).For drugs with this basic structure,the substituents on the heterocyclic ring determine the pharmacologic class,either anti-MES or antipentylenetetrazol.Very small changes in structure can dramatically alter the mechanism of action and clinical properties of the compound.The remaining drugs%4carbamazepine,valproic acid,and the benzodiazepines%are structurally dissimilar,as are the newer compounds marketed since 1990,ie,felbamate,gabapentin,lamotrigine,levetiracetam,oxcarbazepine, pregabalin,tiagabine,topiramate,vigabatrin,and zonisamide.repeated episodes of focal electrical stimulation) probably provide a better screen for predicting efficacy in complex partial seizures. Existing antiseizure drugs provide adequate seizure control in about two thirds of patients. A fraction of the epileptic population is resistant to all available drugs, and this may be due to increased expression of the multidrug transporter P-glycoprotein 170, a product of the ABCB1 gene. In children, some severe seizure syndromes associated with progressive brain damage are very difficult to treat. In adults, some focal seizures are refractory to medications. Some, particularly in the temporal lobe, are amenable to surgical resection. Some of the drug-resistant population may respond to vagus-nerve stimulation (VNS), a nonpharmacologic treatment for epilepsy now widely approved for treatment of patients with partial seizures. VNS is indicated for refractory cases or for patients in whom antiseizure drugs are poorly tolerated. Stimulating electrodes are implanted in the left vagus nerve, and the pacemaker is implanted in the chest wall or axilla. Use of this device may permit seizure control with lower doses of drugs. New antiseizure drugs are being sought not only by the screening tests noted above but also by more rational approaches. Compounds are sought that act by one of three mechanisms: (1) enhancement of GABAergic (inhibitory) transmission, (2) diminution of excitatory (usually glutamatergic) transmission, or (3) modification of ionic conductances. I. BASIC PHARMACOLOGY OF ANTISEIZURE DRUGS Chemistry Until 1990, approximately 16 antiseizure drugs were available, and 13 of them can be classified into five very similar chemical groups: barbiturates, hydantoins, oxazolidinediones, succinimides, and acetylureas. These groups have in common a similar heterocyclic ring structure with a variety of substituents (Figure 24-1). For drugs with this basic structure, the substituents on the heterocyclic ring determine the pharmacologic class, either anti-MES or antipentylenetetrazol. Very small changes in structure can dramatically alter the mechanism of action and clinical properties of the compound. The remaining drugs¾carbamazepine, valproic acid, and the benzodiazepines¾are structurally dissimilar, as are the newer compounds marketed since 1990, ie, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, vigabatrin, and zonisamide