Epilepsia
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Review Comparative Study
Comparative anticonvulsant and mechanistic profile of the established and newer antiepileptic drugs.
Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory-mediated neurotransmission, or reduction of excitatory-mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic-based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. ⋯ FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA- and AMPA/kainate-mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.
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Gabapentin, in clinical use since 1993, is indicated as an adjunctive antiepileptic drug (AED) for treatment of complex partial seizures, with or without secondary generalization, in patients over 12 years of age. Although several cellular actions have been described in the literature, the molecular mechanism(s) of action responsible for the anticonvulsant effect of gabapentin has not been conclusively determined. It is likely that gabapentin has multiple concentration-dependent actions that combine in a unique manner to produce antiepileptic efficacy. ⋯ To date, nearly 3 million patients have been treated in studies and in open use without causal relationship to a specific life-threatening organ toxicity. Seizure control superior to that observed in well-controlled trials has been reported at higher doses used in clinical practice and in studies. Therefore, gabapentin dosing must be optimized on an individual basis to achieve an adequate trial of the drug and obtain the best seizure control.
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To determine whether neurochemical activation of the N-methyl-D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 11C-labeled (S)-[N-methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE). ⋯ Radioactivity uptake of intravenously administered (S)-[N-methyl-11C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion, focal atrophy, or other factors.