A new approach to the modulation of GABA(A) receptors

E. Costa, A. Guidotti, A. Kozikowski, D. Ma

Research output: Contribution to journalArticlepeer-review

Abstract

Novelty: Novel 2-aryl-3-indoleacetamide derivatives are claimed. The compounds bind to the mitochondrial BZ recognition site but not to the BZ receptor site located on the GABA(A) receptor complex. They are potentially useful as anxiolytic agents and for the treatment of schizophrenia, depression and Parkinson's disease. Biology: Compounds were screened in a range of receptor binding assays. The preferred compound displaced [3H]-PK11195 and [3H]-Ro5-4864 binding with IC50 values of 18 and 20 nM respectively, and stimulated pregenolone formation in glial mitochondria with EC50 values of 3.3 x 10-9 M. Anxiolytic activity was investigated using an elevated X Maze test. The preferred compound was effective at a dose of 0.5 mg/kg iv. Chemistry: Twenty-one compounds are exemplifed by synthesis using standard methodology. N,N-Di-n-hexyl-2-(4-fluorophenyl)-3-indoleacetamide is one of three specifically claimed compounds.

Original languageEnglish (US)
Pages (from-to)633-635
Number of pages3
JournalCurrent Opinion in Therapeutic Patents
Volume3
Issue number5
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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