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-tet rahydroacridine [bis (7)-tacrine], a novel dimeric acetylcholinesterase inh ibitor (AChEI) derived from 9-amino-1,2,3, 4-tetrahydroaminoacridine (tacri ne), 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 wate r maze was measured to evaluate performance. Tacrine was used as a referenc e 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 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 mu mol.kg(-1), ig or ip) to shorten the escape latenc y was 24 or 12 times of tacrine (8.52 mu mol.kg(-1) ig, 4.26 mu mol. kg(-1) ip) following ig or ip administration, respectively. There appeared to be an inverse bell-shape dose-dependent effect for both compounds tested. CONC LUSION: Bis (7)-tacrine is a more potent and orally active AChEI than tacri ne, and has potential for the palliative treatment of Alzheimer disease.