| Title : Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist - Li_1999_Neuroreport_10_795 |
| Author(s) : Li CY , Wang H , Xue H , Carlier PR , Hui KM , Pang YP , Li ZW , Han YF |
| Ref : Neuroreport , 10 :795 , 1999 |
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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 Ki of 6.0 microM; 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 microM, 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. |
| PubMedSearch : Li_1999_Neuroreport_10_795 |
| PubMedID: 10208550 |
| Inhibitor | Bis7-tacrine |
Li CY, Wang H, Xue H, Carlier PR, Hui KM, Pang YP, Li ZW, Han YF (1999)
Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor antagonist
Neuroreport
10 :795
Li CY, Wang H, Xue H, Carlier PR, Hui KM, Pang YP, Li ZW, Han YF (1999)
Neuroreport
10 :795