Anticonvulsant properties of 3-hydroxy-2-quinoxalinecarboxylic acid, a newly found antagonist of excitatory amino acids.
Various aromatic acids have been investigated as putative ligands of excitatory amino acid receptors. 3-Hydroxy-2-quinoxalinecarboxylic acid (HQC), at 1 mM, was found to antagonize the 22Na+ efflux produced in 22Na+-preloaded brain slices by N-methyl-D-aspartate and kainate. The response to glutamate was also affected but not that to quisqualate. The apparent KI value of HQC for suppression of the N-methyl-D-aspartate response was 0.27 mM. The anticonvulsant action of HQC was investigated in mice and rats. HQC administered intracerebroventricularly caused a dose dependent delay in the occurrence of picrotoxin induced convulsions and afforded protection against picrotoxin induced death. These results confirm the proposition that antagonists of excitatory amino acids possess anticonvulsant properties.
Erez
U
U
Frenk
H
H
Goldberg
O
O
Cohen
A
A
Teichberg
V I
VI
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D018698:Glutamic Acid; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate; D010852:Picrotoxin; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D001224:Aspartic Acid; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007608:Kainic Acid; D016202:N-Methylaspartate; D010852:Picrotoxin; D011759:Pyrrolidines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D012964:Sodium; C045596:3-hydroxy-2-quinoxalinecarboxylic acid