title: Mechanisms of action of currently prescribed and newly developed antiepileptic drugs.
abstract: Clinically available antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium (Na) channels, gamma-aminobutyric acid A (GABAA) receptors, or calcium (Ca) channels. Benzodiazepines and barbiturates enhance GABAA-receptor-mediated inhibition. Phenytoin, carbamazepine and, possibly, valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing Na channel inactivation. Ethosuximide and VPA reduce a low threshold (T-type) Ca-channel current. The mechanisms of action of recently developed AEDs are less clear. Lamotrigine may decrease sustained high-frequency repetitive firing of voltage-dependent Na action potentials, and gabapentin (GBP) appears to bind to a specific binding site in the CNS with a restricted regional distribution. However, the identity of the binding site and the mechanism of action of GBP remain uncertain. The antiepileptic effect of felbamate may involve interaction at the strychnine-insensitive glycine site of the N-methyl-D-aspartate receptor, but the mechanism of action is not yet proven.
authors.affiliation: Department of Neurology, University of Michigan Medical School, Ann Arbor.
authors.forename: R L
authors.initials: RL
authors.lastname: Macdonald
authors.forename: K M
authors.initials: KM
authors.lastname: Kelly
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy*; D000078328:Felbamate; D000077206:Gabapentin; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D000077213:Lamotrigine; D051379:Mice; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid
chemical_list: D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D015507:Drugs, Investigational; D007473:Ion Channels; D048448:Phenylcarbamates; D011409:Propylene Glycols; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014227:Triazines; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin; D000077213:Lamotrigine; D000078328:Felbamate