The mechanisms of antiepileptic drug action are reviewed from the University Pediatric Epilepsy Program and Division of Pediatric Neurology, University of Minnesota Hospital, Minneapolis, MN. Phenytoin, carbamazepine, and valproic acid decrease sustained repetitive firing of action potentials at therapeutic concentrations. Unlike phenytoin and carbamazepine which block the sodium channel, valproic acid blocks sustained repetitive firing by activation of calcium-dependent, potassium conductance. Phenytoin and carbamazepine also have the ability to block post-tetanic potentiation, an effect mediated by blocking the sodium channel. Benzodiazepines and barbiturates enhance GABA-mediated inhibition. Other mechanisms of antiepileptic drug action include inhibition of calcium influx, inhibition of excitatory receptors, or excitation of inhibitory receptors. Glutamate and aspartate are the major excitatory neurotransmitters in the central nervous system and glutamate binds to excitatory receptors, including N-Methyl D-aspartate (NMDA). NMDA receptors which regulate channels permeable to sodium and calcium and are blocked by magnesium play a role in the pathogenesis of some forms of epilepsy. Lamotrigine is an NMDA antagonist with antiepileptic potential. [1]

COMMENT. This excellent review of antiepileptic drug action might also include acetazolamide, a carbonic anhydrase inhibitor with an anticonvulsant mechanism that is unique and not shared by the drugs noted in the review. Acetazolamide is a sulfonamide containing a free-S02NH2 group which is essential for inhibition of carbonic anhydrase. The anticonvulsant effect of acetazolamide is not abolished by nephrectomy and is independent of the action of the drug on the kidney and the resultant metabolic acidosis. The anticonvulsant effect is correlated directly with the inhibition of brain carbonic anhydrase [2] The inhibition of carbonic anhydrase located in glial cells results in CO2 accumulation and changes in acid-base and electrolyte balance that reduce neuronal excitability.