6533b7d6fe1ef96bd1265d9c

RESEARCH PRODUCT

Novel Potent Anticonvulsant Agent Containing a Tetrahydroisoquinoline Skeleton

Alba ChimirriRita CitraroRoberta CarusoRosaria GittoEmilio RussoGiovambattista De SarroLaura De LucaBenedetta Pagano

subject

MaleStereochemistrymedicine.medical_treatmentAMPA receptorIn Vitro TechniquesChemical synthesisMiceStructure-Activity Relationshipchemistry.chemical_compoundPiperidinesSeizuresTetrahydroisoquinolinesAMPADrug DiscoverymedicineAnimalsPotencyReceptors AMPARats WistarTalampanelTetrahydroisoquinolineAntagonistAMPA; Isoquinolines; anticonvulsantsOlfactory PathwaysIsoquinolinesRatsAnticonvulsant AgentAnticonvulsantAcoustic StimulationchemistryMice Inbred DBAMolecular MedicineAnticonvulsants

description

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 against audiogenic 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 only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.

yearjournalcountryeditionlanguage
2006-01-01
http://hdl.handle.net/10447/31865