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The next generation of cholinesterase inhibitors

Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. The biochemical effects of these drugs on plasma cholinesterase activity and cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. It is possible that some of these analogues with more potent cholinergic effect than THA might be the next generation of cholinesterase inhibitors which can be useful in the treatment of Alzheimer's disease.