Bis(7)-tacrine, a novel acetylcholinesterase inhibitor, reverses AF64A-induced deficits in navigational memory in rats.
The novel dimer bis(7)-tacrine (1,7-N-Heptylene-bis-9,9'-amino-1,2,3, 4-tetrahydroacridine), which exhibits higher potency, selectivity and oral activity on acetylcholinesterase inhibition in vivo than tacrine, was evaluated for its ability to reverse AF64A-induced spatial memory impairment in rats using the Morris water maze. The intracerebroventricular injection of AF64A (3 nmol/side) resulted in a substantial increase in the escape latency to find the platform (F(1,7)=30.2, P<0.01). The observed impairment of spatial memory was paralleled by a 47% decrease in choline acetyltransferase activity in the hippocampus. Oral administration of bis(7)-tacrine (0.22-0.89 micromol/kg) dose-dependently reversed the AF64A-induced latency delay to the level of the saline control group (F(4,28)=7.45, P<0. 05). The present study provides additional evidence of bis(7)-tacrine as an ideal candidate for the palliative treatment of Alzheimer's disease.
Liu
J
J
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Ho
W
W
Lee
N T
NT
Carlier
P R
PR
Pang
Y
Y
Han
Y
Y
D000818:Animals; D001388:Aziridines / Q000008:administration & dosage; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004924:Escape Reaction / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014118:Toxins, Biological / Q000008:administration & dosage
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D001388:Aziridines; D002800:Cholinesterase Inhibitors; D014118:Toxins, Biological; D013619:Tacrine; C044894:ethylcholine aziridinium; D002794:Choline