NMDA antagonists differentiate epileptogenesis from seizure expression in an in vitro model.
In an electrographic model of seizures in the hippocampal slice, both of the N-methyl-D-aspartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid and 5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) prevented the progressive development of seizures but did not block previously induced seizures. Thus, a process dependent on the NMDA receptor-ionophore complex establishes a long-lasting, seizure-prone state; thereafter the seizures depend on non-NMDA receptor-ionophore mechanisms. This suggests that there is an important distinction between epileptogenesis and seizure expression and between antiepileptogenic and anticonvulsant pharmacological agents.
Stasheff
S F
SF
Epilepsy Center, Veterans Administration Medical Center, Durham, NC 27705.
Anderson
W W
WW
Clark
S
S
Wilson
W A
WA
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D004558:Electric Stimulation; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials; D006624:Hippocampus / Q000503:physiopathology*; D066298:In Vitro Techniques; D016202:N-Methylaspartate; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D014633:Valine