Attenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine, a novel dimeric AChE inhibitor.
OBJECTIVE
To study the effects of 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine [bis(7)-tacrine], a novel dimeric acetylcholine-sterase inhibitor (AChEI) derived from 9-amino-1,2,3,4-tetrahydroaminoacridine (tacrine), on scopolamine-induced spatial memory impairment.


METHODS
The effects of bis(7)-tacrine were investigated on the 5-d performance of young adult rats in the Morris water maze. The latency to find the platform in the water maze was measured to evaluate performance. Tacrine was used as a reference drug.


RESULTS
Scopolamine (0.3 mg.kg-1, i.p.) resulted in an increase in latency period (> 100% increase) as compared with saline treated controls. Both bis(7)-tacrine and tacrine lessened the increased latency induced by scopolamine to the level of saline control group. The relative potency of bis(7)-tacrine (0.35 mumol.kg-1, i.g. or i.p.) to shorten the escape latency was 24 or 12 times of tacrine (8.52 mumol.kg-1 i.g., 4.26 mumol.kg-1 i.p.) following i.g. or i.p. administration, respectively. There appeared to be an inverse bell-shape dose-dependent effect for both compounds tested.


CONCLUSIONS
Bis(7)-tacrine is a more potent and orally active AChEI than tacrine, and has potential for the palliative treatment of Alzheimer disease.
Wang
H
H
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, China.
Carlier
P R
PR
Ho
W L
WL
Lee
N T
NT
Pang
Y P
YP
Han
Y F
YF
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D013619:Tacrine; D012601:Scopolamine