| Abstract
| - In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure−activity relationships. All derivatives were evaluated againstaudiogenic seizures in DBA/2 mice, and the 1-(4‘-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl)derivative (26) showed the highest activity with a potency comparable to that of talampanel, the onlynoncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trialsas an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPAreceptor modulator.
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