Effect of 2-amino-7-phosphonoheptanoic acid (APH) on seizure susceptibility in the prepubescent and mature rat.
There is now considerable evidence that the N-methyl-D-aspartic acid receptor is important in the genesis of seizures. One of the selective antagonist of the NMDA receptor is 2-amino-7-phosphonoheptanoic acid (APH). In this study we evaluated the effects of intracerebroventricular (i.c.v.) administration of APH on seizure susceptibility in both prepubescent and mature rats using the rapid kindling and flurothyl ether seizure models. Both the immature and mature animals receiving APH kindled at a significantly slower rate than control animals receiving phosphate-buffered saline. APH also demonstrated a significant anticonvulsant effect against flurothyl-induced seizures in both the immature and mature animals. This study supports prior work that selective NMDA receptor antagonists such as APH may have promise as potential antiepileptic agents.
Holmes
G L
GL
Department of Neurology, Children's Hospital, Boston, MA 02115.
Thompson
J L
JL
Carl
G F
GF
Gallagher
B S
BS
Hoy
J
J
McLaughlin
M
M
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid