Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist

Li Chao Ying, Hong Wang, Hong Xue, Paul R. Carlier, Kowk Min Hui, Yuan Ping Pang, Zhi Wang Li, Yi Fan Han

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) (bis(7)- tacrine) is a potential palliative therapeutic agent for Alzheimer's disease (AD), on the basis of its superior acetylcholinesterase (ACHE) inhibition and memory-enhancing potency relative to tacrine. In this study we report that bis(7)-tacrine exhibits a potentially complementary central nervous system action, antagonism of GABA(A) receptor function. Bis(7)tacrine displaced [3H]muscimol from rat brain membranes with an apparent K(i) of 6.0 μM; tacrine and physostigmine were shown to be 18 and 170 times less potent, respectively. In whole-cell patch-clamp recordings, bis(7)-tacrine inhibited GABA-induced inward current with an IC50 of 5.6 μM, and shifted the GABA concentration-response curve to the right in a parallel manner. These results suggest that bis(7)-tacrine is a competitive antagonist of the GABA(A) receptor.

Original languageEnglish (US)
Pages (from-to)795-800
Number of pages6
JournalNeuroReport
Volume10
Issue number4
StatePublished - Mar 17 1999

Keywords

  • Acetylcholinesterase
  • Bis(7)-tacrine
  • Cholinesterase inhibitor
  • GABA(A) receptor
  • Muscimol
  • Physostigmine
  • Tacrine

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chao Ying, L., Wang, H., Xue, H., Carlier, P. R., Min Hui, K., Ping Pang, Y., Wang Li, Z., & Fan Han, Y. (1999). Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist. NeuroReport, 10(4), 795-800.