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 Citations (Scopus)

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 IC 50 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

Fingerprint

GABA-A Receptor Antagonists
Tacrine
gamma-Aminobutyric Acid
Muscimol
Physostigmine
GABA-A Receptors
Acetylcholinesterase
Alzheimer Disease
Central Nervous System
1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
Membranes
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist. / Chao Ying, Li; Wang, Hong; Xue, Hong; Carlier, Paul R.; Min Hui, Kowk; Pang, Yuan-Ping; Wang Li, Zhi; Fan Han, Yi.

In: NeuroReport, Vol. 10, No. 4, 17.03.1999, p. 795-800.

Research output: Contribution to journalArticle

Chao Ying, L, Wang, H, Xue, H, Carlier, PR, Min Hui, K, Pang, Y-P, Wang Li, Z & Fan Han, Y 1999, 'Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist', NeuroReport, vol. 10, no. 4, pp. 795-800.
Chao Ying L, Wang H, Xue H, Carlier PR, Min Hui K, Pang Y-P et al. Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist. NeuroReport. 1999 Mar 17;10(4):795-800.
Chao Ying, Li ; Wang, Hong ; Xue, Hong ; Carlier, Paul R. ; Min Hui, Kowk ; Pang, Yuan-Ping ; Wang Li, Zhi ; Fan Han, Yi. / Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist. In: NeuroReport. 1999 ; Vol. 10, No. 4. pp. 795-800.
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