title: Comparison of the effects of cholinesterase inhibitors on [3H]MK-801 binding in rat cerebral cortex.
abstract: Huperzine A, a selective inhibitor of acetylcholinesterase, was recently demonstrated to exert an antagonist effect on N-methyl-D-aspartate (NMDA) receptor in rat cerebral cortex. In the present study, the effects of six cholinesterase inhibitors, e.g. huperzine A, huperzine B, tacrine, donepezil (E2020), physostigmine and galanthamine on [3H]dizocilpine (MK-801) binding to synaptic membrane of rat cerebral cortex were compared. Their IC50 values (mean +/- SD) were 36.9 +/- 12.1, 316.8 +/- 93.2, 33.2 +/- 3.7, 135.0 +/- 15.1, 50.4 +/- 7.4, and 3344 +/- 295 microM, respectively. The rank order of potency is tacrine approximately huperzine A > physostigmine > donepezil > huperzine B >> galanthamine. There is no correlation between their activities to inhibit [3H]MK-801 binding and to inhibit acetylcholinesterase (r = +0.563, P = 0.245). The results suggest that most cholinesterase inhibitors available exhibit an antagonist effect on NMDA receptor in rat cerebral cortex in addition to their inhibitory effect on acetylcholinesterase.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
authors.forename: X D
authors.initials: XD
authors.lastname: Wang
authors.forename: X Q
authors.initials: XQ
authors.lastname: Chen
authors.forename: H H
authors.initials: HH
authors.lastname: Yang
authors.forename: G Y
authors.initials: GY
authors.lastname: Hu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate