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 μmol/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. (C) 2000 Elsevier Science Ireland Ltd.