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.
Ashton
D
D
Department of Neuropharmacology, Janssen Research Foundation, Beerse, Belgium.
Willems
R
R
De Prins
E
E
Wauquier
A
A
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004558:Electric Stimulation; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D000596:Amino Acids; D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid