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An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action Shank RP; Gardocki JF; Streeter AJ; Maryanoff BEEpilepsia 2000[]; 41 (S1): 3-9In this overview, we discuss the discovery and development of topiramate (TPM) as an anticonvulsant, including notable aspects of its chemical, biologic, and pharmacokinetic properties. In particular, we highlight its anticonvulsant profile in traditional seizure tests and animal models of epilepsy and the results of recent electrophysiological and biochemical studies using cultured neurons that have revealed a unique combination of pharmacologic properties of TPM. Finally, we present a hypothesis for the mechanistic basis of the anticonvulsant activity of TPM, which proposes that TPM binds to certain membrane ion channel proteins at phosphorylation sites and thereby allosterically modulates channel conductance and secondarily inhibits protein phosphorylation.|Animals[MESH]|Anticonvulsants/*pharmacokinetics/*pharmacology/therapeutic use[MESH]|Calcium Channels/drug effects[MESH]|Disease Models, Animal[MESH]|Epilepsy/drug therapy/prevention & control[MESH]|Evoked Potentials/drug effects[MESH]|Fructose/*analogs & derivatives/pharmacokinetics/pharmacology/therapeutic use[MESH]|Hippocampus/drug effects[MESH]|Humans[MESH]|Male[MESH]|Membrane Potentials/drug effects[MESH]|Mice[MESH]|Patch-Clamp Techniques[MESH]|Phosphorylation/drug effects[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Receptors, AMPA/antagonists & inhibitors/drug effects[MESH]|Receptors, GABA/drug effects[MESH]|Receptors, Kainic Acid/antagonists & inhibitors/drug effects[MESH]|Sodium Channel Blockers[MESH]|Sodium Channels/drug effects[MESH]|Topiramate[MESH] |
