[GABA-ergic system and antiepileptic drugs]

gamma-Aminobutyric acid (GABA) belongs to main inhibitory neurotransmitters in the central nervous system and activates three types of specific receptors--GABAA, GABAB i GABAC. At present, little is known about GABAC-mediated events. GABAB receptors are metabotropic, whilst stimulation of ionotropic GABAA receptors results in opening the chloride channel, followed by influx of chloride ions and hyperpolarization. The GABAA receptor possesses also binding sites for benzodiazepines and barbiturates which, via these sites, enhance GABAA-mediated events. Another antiepileptic drug potentiating GABA-ergic inhibition is valproate, which increases synthesis of GABA and reduces its metabolism. Among new antiepileptic drugs associated with the GABA-ergic system are tiagabine, vigabatrin, and to a certain degree--gabapentin. Tiagabine blocks neuronal and glial uptake of GABA whilst vigabatrin increases the synaptic concentration of GABA by inhibition of GABA aminotransferase. Gabapentin, probably through the activation of glutamic acid decarboxylase, leads to the increase in synaptic GABA. However, this antiepileptic drugs is also binds to specific sites within voltage-dependent calcium channels, which results in the reduced intraneuronal concentration of calcium ions. Presumably, tiagabine and vigabatrin possess only one mechanism of action, associated with the increased GABA-ergic inhibition. Although topiramate and felbamate were shown to enhance GABA-mediated events, they have additional mechanisms of action, including blockade of voltage-dependent sodium channels and inhibition of glutamatergic neurotransmission.