A benzodiazepine recognition site associated with the non-NMDA glutamate receptor

Charles F. Zorumski, Kelvin A. Yamada, Madelon T. Price, John W. Olney

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

GYKI 52466 is a benzodiazepine molecule that has muscle relaxant and anticonvulsant properties not attributable to a γ-aminobutyric acid receptor-mediated mechanism. Here it is shown that GYKI 52466 exerts no blocking action at N-methyl-d-aspartate (NMDA) glutamate receptors, but acts noncompetitively to block ion currents and associated excitotoxicity, including ischemic neuronal degeneration, mediated through non-NMDA glutamate receptors. The inhibition of non-NMDA responses by GYKI 52466 is antagonized by cyclothiazide, hydrochlorothiazide, and diazoxide, benzothiadiazide drugs that inhibit non-NMDA receptor desensitization. These results suggest that non-NMDA receptor-ion channel complexes may contain a novel benzodiazepine recognition site where receptor desensitization is regulated; this postulated site represents a promising new target for rational development of drugs to treat neurological disorders.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalNeuron
Volume10
Issue number1
DOIs
StatePublished - Jan 1993

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