COMPARATIVE-STUDIES OF HUPERZINE-A, E2020, AND TACRINE ON BEHAVIOR AND CHOLINESTERASE ACTIVITIES

Comparative effects of cholinesterase inhibitors (ChEI) huperzine A wi th E2020 and tacrine on the radial maze performance in ethylcholine mu stard aziridinium ion (AF64A)-treated rat and inhibition of cholineste rase activity were studied. The intracerebroventricular (ICV) injectio n of AF64A (3 nmol/side) caused significant impairment in the rat's ab ility to fulfill the partially baited maze paradigm. Oral huperzine A (0.5-0.8 mg/kg), E2020 (1.0-2.0 mg/kg), and tacrine (8.0 mg/kg) effect ively reversed AF64A-induced working memory deficit. The doses that im proved AFB4A-induced memory deficit were correlated to about 25-30% (h uperzine A) and less than 10% (E2020, tacrine) inhibition of acetylcho linesterase (AChE) activity in the cortex and hippocampus. Huperzine A , E2020 and tacrine all produced dose-dependent inhibition of brain AC hE following ICV and oral administration. Oral huperzine A exhibited h igher efficacy on the inhibition of AChE in the cortex and hippocampus than those of E2020 and tacrine. Tacrine was more effective in inhibi ting plasma butyrylcholinesterase (BuChE) than it was brain AChE. Conv ersely, the BuChE activity was less affected by huperzine A and E2020. The results showed that huperzine A had high bioavailability and more selective inhibition on AChE activity in cortex and hippocampus. Hupe rzine A fits more closely with the established criteria for an ideal A ChE inhibitor to be used in clinical studies. (C) 1998 Elsevier Scienc e Inc.