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)-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
H
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay.
Carlier
P R
PR
Ho
W L
WL
Wu
D C
DC
Lee
N T
NT
Li
C P
CP
Pang
Y P
YP
Han
Y F
YF
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase