title: Anticonvulsant, antiepileptogenic, and antiictogenic pharmacostrategies.
abstract: Pharmacological concepts tailored to status epilepticus, to epileptogenesis following acquired brain insults, and to ictogenesis in established epilepsy vary considerably and should ideally be directed at those pathophysiological mechanisms that presumably underly these conditions. Currently known important molecular targets include voltage-gated sodium and calcium channels, the gamma-aminobutyric acid (GABA) system and ionotropic glutamate receptors. Metabotropic glutamate receptors, potassium channels, and neurotransmitters such as acetylcholine, glycine, and monoamines are beyond the scope of this review. In status epilepticus, immediate failure of GABAergic inhibition occurs, and administration of benzodiazepines and barbiturates displays the pharmacostrategic mainstay. In epileptogenesis within limbic structures, the most important underlying pathophysiological mechanisms currently discussed are transient loss of inhibition and aberrant mossy fiber sprouting. Both processes may be facilitated by N-methy-D: -aspartat (NMDA) receptor regulation. NMDA antagonists may exhibit antiepileptogenic properties in experimental animals, but reliable data in humans are lacking. In established epilepsy, voltage-gated ion channels and impairment of GABAergic functions contribute to mechanisms facilitating ictogenesis. Blockade of sodium and calcium channels and enhancement of GABAergic inhibition are currently the most important tools to prevent the occurrence of seizures.
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin (Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany. martin.holtkamp@charite.de
authors.forename: M
authors.initials: M
authors.lastname: Holtkamp
authors.forename: H
authors.initials: H
authors.lastname: Meierkord
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D018079:Receptors, GABA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D013226:Status Epilepticus / Q000188:drug therapy; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D015220:Calcium Channels; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D005680:gamma-Aminobutyric Acid