Attenuation of febrile seizures in epileptic chicks by N-methyl-D-aspartate receptor antagonists.
Experimental febrile seizures can be evoked in epileptic chicks by elevation of their body temperature. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(+/- )2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), DL-2-amino-7-phosphosphonoheptanoic acid (APH), DL-2-amino-5-phosphonovaleric acid (APV), D-alpha-aminoadipic acid (AAA), and DL-alpha, epsilon-diaminopimelic acid (DAP)] and the noncompetitive NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5, 10-imine maleate (MK-801) produced dose-dependent increases in latency to the onset of seizures. Of the drugs tested, MK-801 had the highest potency followed in order by CPP = APH greater than APV much greater than AAA greater than DAP. There was a high correlation (r = 0.995) between the dose capable of doubling seizure latency and the affinity of the competitive NMDA antagonists for the NMDA receptor as determined by in vitro binding assays. These data suggest that NMDA receptor mediated mechanisms may be involved in the production of seizures in response to hyperthermia.
Pedder
S C
SC
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Wilcox
R I
RI
Tuchek
J M
JM
Johnson
D D
DD
Crawford
R D
RD
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002645:Chickens; D003960:Diaminopimelic Acid / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D005334:Fever / Q000150:complications*; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D013570:Synaptic Membranes / Q000502:physiology
D000596:Amino Acids; D003986:Dibenzocycloheptenes; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015074:2-Aminoadipic Acid; D003960:Diaminopimelic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C031231:2-amino-7-phosphonoheptanoic acid