Selective inhibition of synaptic versus non-synaptic epileptogenesis by NMDA antagonists in the in vitro hippocampus.

Three NMDA antagonists (2-amino-7-phosphonoheptanoic acid (APH), MK-801, and ketamine) were tested for their ability to antagonize epileptogenic responses in a synaptic and a non-synaptic model of epileptogenesis in the CA1 region of the hippocampal slice. IC50 values for antagonism of the second population spike in the 'low Mg2+' synaptic model were MK-801 1.5 x 10(-7) M, APH 7.4 x 10(-7) M, ketamine 7.5 x 10(-7) M. IC50 values for antagonism of the frequency of spontaneous field bursts in the non-synaptic 'low Ca2+' model were MK-801 3.2 x 10(-5) M, ketamine 3.2 x 10(-5) M and APH greater than 10(-4) M. The antiepileptogenic action of NMDA antagonists is therefore more pronounced in the model with an important involvement of the NMDA receptor ionophore.