Effects of naftidrofuryl oxalate (LS-121) on experimental amnesia models, which were induced by cycloheximide (CXM), scopolamine (SLOP) and basal-forebrain (BF) lesion, were investigated using the step-through passive avoidance response in rats. In the retention test, a cut-off time of 600 sec was employed for the measurement of step-through latency (STL). The animals, that showed over 300 sec of STL was regarded as having the criterion of memory retention (% of retention). Increase in both parameters of STL and % of retention was regarded to indicate that the drug was able to improve the amnesia. If only one of the two parameters was increased, we considered that the drug had a tendency to improve the amnesia. Pretraining, post-training and pre-retention treatment of LS-121 (25 mg/kg) improved CXM-and SLOP-induced amnesia. Post-training treatment of LS-121 (25 mg/kg) showed a tendency to improve the BF lesion-induced amnesia. These results suggest that the antiamnesic action of LS-121 may be produced through an activation of the acetylcholinergic neuronal system. Since it improved the amnesia when administered in the pre-retention test, there is a possibility that LS-121 has not only a protective effect, but also a therapeutic effect. Furthermore, it is suggested that LS-121 may also have a therapeutic effect on Alzheimer's disease, since it showed a tendency to improve the BF lesion-induced amnesia.
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