Attenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine, a novel dimeric AChE inhibitor

AIM: To study the effects of 1,7-N-heptylene-bis-9,9'-amino-1,2, 3,4- tetrahydroacridine [bis (7)-tacrine], a novel dimeric acetylcholinesterase 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. Tactine was used as a reference drug. RESULTS: Scopolamine (0.3 mg · kg-1, ip) resulted in an increase in latency period (> 100 % increase) as compared with saline treated controls. Both his (7)-tacrine and tactine lessened the increased latency induced by scopolamine to the level of saline control group. The relative potency of his (7)-tacrine (0.35 μmol · kg-1, ig or ip) to shorten the escape latency was 24 or 12 times of tactine (8.52 μmol · kg-1ig, 4.26 μmol · kg-1ip) following ig or ip administration, respectively. There appeared to be an inverse bell-shape dose-dependent effect for both compounds tested. CONCLUSION: Bis (7)-tacrine is a more potent and orally active AChEI than tactine, and has potential for the palliative treatment of Alzheimer disease.