Abstract: Coupled to the N-methyl-D-aspartate (NMDA) receptor complex is a strychnine-insensitive binding site for glycine. Pharmacological antagonism of glycine at this site may produce anticonvulsant activity. Twelve 4-urea-5,7-dichlorokynurenic acid derivatives were synthesized and subsequently screened in mice for anticonvulsant activity using MES, Met, and TTE tests, and a rotorod test was used to determine neurotoxicity. Seven of the derivatives had anticonvulsant activity in TTE testing at 100 mg/kg. One derivative had an ED.sub.50 value of 134 mg/kg in TTE testing. Two derivatives had MES activity. Only one derivative was neurotoxic in the rotorod test. Compounds were screened at a 10 uM concentration for activity in displacing 5,7-dichlorokynurenic acid from synaptosomal membrane fragments. Nine of the twelve compounds synthesized and tested have demonstrated anticonvulsant activity.

Abstract: Coupled to the N-methyl-D-aspartate (NMDA) receptor complex is a strychnine-insensitive binding site for glycine. Pharmacological antagonism of glycine at this site may produce anticonvulsant activity. Twelve 4-urea-5,7-dichlorokynurenic acid derivatives were synthesized and subsequently screened in mice for anticonvulsant activity using MES, Met, and TTE tests, and a rotorod test was used to determine neurotoxicity. Seven of the derivatives had anticonvulsant activity in TTE testing at 100 mg/kg. One derivative had an ED.sub.50 value of 134 mg/kg in TTE testing. Two derivatives had MES activity. Only one derivative was neurotoxic in the rotorod test. Compounds were screened at a 10 uM concentration for activity in displacing 5,7-dichlorokynurenic acid from synaptosomal membrane fragments. Nine of the twelve compounds synthesized and tested have demonstrated anticonvulsant activity.

Abstract: Coupled to the N-methyl-D-aspartate (NMDA) receptor-channel complex is a strychnine-insensitive binding site for glycine. Pharmacological antagonism of glycine binding at this site can produce anticonvulsant activity. Derivatives of kynurenic acid, pyridine and 2-carboxy-indole were synthesized and evaluated as antagonists of glycine binding and for anticonvulsant effects. Compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole, and in the rotorod assay for neurologic deficit. The derivatives were also assayed for binding at the NMDA-associated glycine site. The most potent anticonvulsant was ethyl 4-methylamino-5,7-dichloro-2-quinoline carboxylate. This compound provided protection against maximal electroshock (MES) induced seizures at a dose of 30 mg/kg. Other compounds were active at 100 mg/kg dose level, including 5-fluoro-2-indole carboxylic acid and the diethyl ester of 2,6-pyridine dicarboxylic acid.

Abstract: A 7-chloro-4-hydroxy-2-quinoline carbonyl azide and its use as a photoaffinity probe for the N-methyl-D-aspartate (NMDA) receptor complex on neurons are claimed. A number of other compounds, including 4-hydroxy-2-quinoline carbonyl azides, isocyanates, and amides are also provided. Purification and characterization of the NMDA receptor is described.

Abstract: A 7-chloro-4-hydroxy-2-quinoline carbonyl azide and its use as a photoaffinity probe for the N-methyl-D-aspartate (NMDA) receptor complex on neurons are claimed. A number of other compounds, including 4-hydroxy-2-quinoline carbonyl azides, isocyanates, and amides are also provided. Purification and characterization of the NMDA receptor is described.