A NOVEL ANTICHOLINESTERASE THB013 - BIOCHEMICAL AND BEHAVIORAL-STUDIES

Clinical trials with tacrine (THA) have resulted in elevations of live r 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 behavi oural studies. In this study, the biochemical effects of THA and one o f these analogs, THB 013, on plasma cholinesterase activity, cholinerg ic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking t he scopolamine induced disruption of spatial learning when administere d 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.