As a follow up of our previous structure-activity relationship and molecular modeling studies, we synthesized a novel series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as potential non-competitive AMPA receptor antagonists. When tested for their ability to prevent sound-induced seizures in DBA/2 mice, some of these novel compounds showed high anticonvulsant potency.