Anticonvulsants acting on the GABA system

Modification of activity at GABAergic synapses powerfully influences epileptic phenomena. These effects show significant differences according to the type of epilepsy involved. The predominant effect for focal motor and tonic-clonic seizures is that impairment or reduction of function at GABAA receptors facilitates epileptic discharges and motor seizure activity and enhancement of function diminishes epileptic activity. This is clearly a consequence of the role of GABAergic synapses in recurrent inhibitory systems in cortical and other structures, and their effect in limiting the excessive discharge of principal neurons in time and space. Compounds blocking the inhibitory action of GABA at GABAA receptors such as bicuculline and picrotoxin are powerful convulsants when given focally in the brain or systemically. Compounds inhibiting glutamic acid decarboxylase activity thereby blocking GABA synthesis, such as pyridoxal phosphate antagonists, are convulsant (for a more extensive list of epilepsy syndromes and seizures caused by GABA-related mechanisms see Table 1). Compounds potentiating the action of GABA at GABAA receptors are anticonvulsant (see below).