We previously reported that
dehydroevodiamine.HCl (
DHED) has
anticholinesterase and antiamnesic activities. To verify the effects of
DHED on cognitive deficits further, we tested it on the
scopolamine-induced
amnesia model of the rat using the passive avoidance and eight-arm radial maze tests. A single (20 mg/kg p.o.) and repeated (10 mg/kg p.o.) administrations of
DHED could significantly reverse the latency time shortened by
scopolamine (1 mg/kg i.p.) to control level. The impaired spatial working memory induced by
scopolamine (1 mg/kg i.p.) was also improved significantly by a single injection (6.25 mg/kg i.p.) and repeated administrations of
DHED (10 mg/kg p.o.) in the eight-arm radial maze test. In addition, we examined the effects of
DHED on the memory impairment and the histological changes of the brain after unilateral electrolytic lesion of the entorhinal cortex (EC) and
middle cerebral artery occlusion in rats. The cognitive deficits caused by EC lesion and
middle cerebral artery occlusion were improved significantly by repeated administrations of
DHED (6.25 mg/kg i.p.) after EC lesion or ischemic insult once a day for 7 days in the passive avoidance test. Histological analysis showed that the neuronal loss in the
DHED-treated group was notably reduced in the hippocampal area (CA1) of ischemic rats and in the dentate gyrus and hippocampal area (CA1 and CA3) of EC-lesioned rats compared with the nontreated group. The
infarction area was decreased significantly by a single administration of
DHED (6.25 mg/kg i.
p.) 30 min before ischemic insult for 6 h. These results suggest that
DHED might be an effective
drug for not only the
Alzheimer's disease type, but also the vascular type of
dementia.