A dipeptide derived from kainic and L-glutamic acids: a selective antagonist of amino acid induced neuroexcitation with anticonvulsant properties.
The dipeptide N-[[[2'S-(2' alpha, 3' beta, 4' beta)]-2'-carboxy-4'-(1"-methylethenyl)-3'-pyrrolidinyl)acetyl]-L- glutamic acid (6) has been synthesized by a route that involves the selective protection of the alpha-carboxyl function of kainic acid. This dipeptide inhibits the stimulation of Na+ fluxes induced in brain slices by the neuroexcitant N-methyl-D-aspartic acid. Administered intracerebroventricularly, it is also effective in protecting mice from picrotoxin-induced convulsions with an ED50 of 0.17 mumol.
Goldberg
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Teichberg
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D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D002463:Cell Membrane Permeability / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D018698:Glutamic Acid; D007608:Kainic Acid / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000037:antagonists & inhibitors; D010852:Picrotoxin; D016318:Quisqualic Acid; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D012964:Sodium / Q000378:metabolism
D001224:Aspartic Acid; D004151:Dipeptides; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007608:Kainic Acid; D016202:N-Methylaspartate; D010069:Oxadiazoles; D010852:Picrotoxin; D016318:Quisqualic Acid; D012964:Sodium; C047296:gamma-kainylglutamic acid