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-tetr ahydroacrindine), which exhibits higher potency, selectivity and oral activ ity 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 spa tial memory was paralleled by a 47% decrease in choline acetyltransferase a ctivity in the hippocampus. Oral administration of bis(7)-tacrine (0.22-0.8 9 mu mol/kg) dose-dependently reversed the AF64A-induced latency delay to t he level of the saline control group (F(4, 28)= 7.45, P < 0.05). The presen t study provides additional evidence of bis(7)-tacrine as an ideal candidat e for the palliative treatment of Alzheimer's disease. (C) 2000 Elsevier Sc ience Ireland Ltd. All rights reserved.