[GABA(A) benzodiazepine receptors and epilepsy]

GABAA-benzodiazepine receptors and epilepsy. gamma-Aminobutyric acid (GABA) is quantitatively one of the most important neurotransmitters in the central nervous system. Since the predominant action of GABA on neurons is inhibitory, activation of GABA receptors, and especially of GABAA receptors, causes an anticonvulsive effect. GABAA receptors can be activated either directly by GABA or GABA-agonists, or indirectly by allosteric modulation of these receptors. For instance, benzodiazepines enhance the postsynaptic actions of GABA by binding to benzodiazepine receptors which are allosteric modulatory binding sites on GABAA receptors. Conversely, there are compounds which bind to the same benzodiazepine receptors, but reduce the postsynaptic actions of GABA. These compounds cause convulsions and are called "inverse agonists" of the benzodiazepine receptors. Recent evidence indicates the existence of several different benzodiazepine receptor (and, thus, GABAA receptor) subtypes. Since these receptor subtypes exhibit a different regional distribution in the central nervous system, the development of subtype-selective GABAA receptor agonists or benzodiazepine receptor agonists should result in anticonvulsants with less side effects.