Mechanisms of action for the commonly used antiepileptic drugs: relevance to antiepileptic drug-associated neurobehavioral adverse effects.
Antiepileptic drugs exert their anticonvulsant effects by interfering with brain processes that involve structures that are also involved in learning, memory, and emotional behavior. Thus, modulation of ion channels, neurotransmitters, second messengers, and other processes by antiepileptic drugs, although helpful in controlling seizures, can interfere with normal brain function in undesired ways. The specific mechanism(s) of action of an antiepileptic drug can increase the risk for particular types of adverse events. In this review, we examine the cognitive and behavioral effects of antiepileptic drugs in animal models. Although animal studies, in many respects, do not mimic clinical experience, the data suggest a connection between certain mechanisms of antiepileptic action and the occurrence of cognitive adverse effects. Specifically, antiepileptic drugs with traditional gamma-aminobutyric acid (GABA)ergic mechanisms have the most detrimental effects on cognitive function, possibly because they impair attention. Conversely, drugs with the predominant effects at Na+ channels appear to have minimal impact on cognition. Levetiracetam, with its nonconventional GABAergic and Ca2+ channel effects, has shown positive cognitive effects in animal studies. Antiglutamatergic drugs have the potential to be a double-edged sword: they can interfere with consolidation of learning and memory but can also provide neuroprotection in addition to their antiseizure effects.
Sankar
Raman
R
Department of Pediatric Neurology, Room 22474 MDCC, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA. rsankar@ucla.edu
Holmes
Gregory L
GL
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D007858:Learning / Q000187:drug effects*; D001523:Mental Disorders / Q000139:chemically induced*
D000927:Anticonvulsants