NOVEL ANTICHOLINESTERASE AND ANTIAMNESIC ACTIVITIES OF DEHYDROEVODIAMINE, A CONSTITUENT OF EVODIA-RUTAECARPA

To find a new compound with antiamnesic activity, we screened 29 natur al products for their abilities to inhibit acetylcholinesterase and re verse scopolamine-induced amnesia. Among the plants tested Evodia ruta ecarpa Bentham showed a strong inhibitory effect on acetylcholinestera se in vitro and an anti-amnesic effect in vivo. By sequential fraction ation of E. rutaecarpa, the active component was finally identified as dehydroevodiamine hydrochloride (DHED). DHED inhibited acetylcholines terase activity in a dose-dependent and noncompetitive manner. The ICS , value of DHED is 37.8 mu M. A single administration of DHED to rats (6.25 mg/kg) significantly reversed the scopolamine-induced memory imp airment in a passive avoidance test. The antiamnesic effect of DHED wa s more potent than that of tacrine which is the only drug for Alzheime r's disease approved by FDA. This potent antiamnesic effect of DHED wa s thought to be due to the combined effects of acetylcholinesterase in hibition and the known cerebral blood flow enhancement. These results indicate that DHED has novel anticholinesterase and antiamnesic activi ties and might have therapeutic potential in various disorders includi ng Alzheimer's disease.