The anticholinesterase effects of bis(7)-tacrine were compared with tacrine in vitro and in vivo. Based on IC50 ratios, the dimeric analog bis(7)-tacrine was, in a reversible manner, up to 150-fold more potent and 250-fold more selective than tacrine for acetylcholinesterase (AChE) over butyrylcholinesterase (BChE). Following a single oral administration, both bis(7)-tacrine and tacrine produced dose-dependent inhibitions of AChE in rat brain, but bis(7)-tacrine exhibited higher efficacy and AChE/BChE selectivity than tacrine. The anti-AChE efficacy of bis(7)-tacrine was quite similar following an oral or i.p. administration, but tacrine showed much lower efficacy when administered orally than when given i.p. These findings suggest bis(7)-tacrine, a highly potent and selective inhibitor of AChE, can probably be used as an improved drug in the palliative treatment of AD.
Wang H, Carlier PR, Ho WL, Wu DC, Lee NT, Li CP, Pang YP, Han YF (1999) Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE Neuroreport10: 789-93
Wang H, Carlier PR, Ho WL, Wu DC, Lee NT, Li CP, Pang YP, Han YF (1999) Neuroreport10: 789-93