NMDA receptor antagonists attenuate a portion of the penicillin-induced epileptiform burst.
In the CA1 region of the rat hippocampal slice, epileptiform activity was induced by the GABAA antagonist penicillin (PEN, 3.4 mM). The competitive N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-7-phosphonoheptanoate (D-AP7) and D-2-amino-5-phosphonovolerate (D-AP5) attenuated extracellularly recorded evoked burst duration, the number of population spikes per evoked bursts and the frequency of spontaneously occurring bursts, but did not affect the sum of the population spike amplitudes or the evoked burst coastline measures due to increases in amplitude of the remaining secondary population spikes. Intracellular recordings showed that many of the secondary action potentials in the PEN burst were decreased in amplitude and broadened in duration, perhaps due to spike inactivation. D-AP7 allowed these secondary action potentials to increase in amplitude, which could explain the increases in secondary population spike amplitude seen extracellularly. Decrements in stimulus strength can mimic the effect of D-AP7 on PEN bursts. These data suggest that there is a portion of the PEN-induced epileptiform burst which is sensitive to NMDA antagonists.
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Central Nervous System Diseases Research, G.D. Searle & Company, Monsanto Company, St. Louis, MO 63198.
Lanthorn
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology* / Q000031:analogs & derivatives; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010406:Penicillins; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D000596:Amino Acids; D000927:Anticonvulsants; D010406:Penicillins; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid