Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE

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)-tacr ine was, in a reversible manner, up to 150-fold more potent and 250-fold mo re selective than tacrine for acetylcholinesterase (AChE) over butyrylcholi nesterase (BChE). Following a single oral administration, both bis(7)-tacri ne and tacrine produced dose-dependent inhibitions of AChE in rat brain, bu t bis(7)-tacrine exhibited higher efficacy and AChE/BChE selectivity than t acrine. The anti-AChE efficacy of bis(7)-tacrine was quite similar followin g an oral or i.p. administration, but tacrine showed much lower efficacy wh en administered orally than when given i.p. These findings suggest bis(7)-t acrine, a highly potent and selective inhibitor of AChE, can probably be us ed as an improved drug in the palliative treatment of AD. NeuroReport 10:78 9-793 (C) 1999 Lippincott Williams & Wilkins.