Antagonism of non-NMDA receptors inhibits handling-induced, strychnine-potentiated convulsions.
The effects of blockade of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA) and kainate subtypes of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) and compared to the effects of N-methyl-D-aspartate (NMDA) receptor blockade with D-CPPene (D-(E)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylic acid), a competitive NMDA antagonist. Both compounds exerted peak blocking activity 30 min after intraperitoneal administration. Using this pretreatment interval, a dose-response relationship for blocking handling-induced, strychnine-potentiated convulsions was generated for each compound. D-CPPene blocked seizures with an ED50 of 0.72 (0.59-0.87) mg/kg and NBQX blocked seizures with an ED50 of 68.0 (36.72-125.94) mg/kg. These results indicate that both NMDA and non-NMDA subtypes of excitatory amino acid receptors are activated in handling-induced, strychnine-potentiated convulsions.
Sandoz Research Institute Berne Ltd., Switzerland.
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McAllister
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists; D006234:Handling, Psychological; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013331:Strychnine / Q000037:antagonists & inhibitors* / Q000633:toxicity
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D013331:Strychnine; C065286:SDZ EAA 494