Earley W G, Kumar V, Mallamo J P, Subramanyam C, Dority J A, Miller M S, DeHaven-Hudkins D L, Aimone L D, Kelly M D, Ault B
Department of Medicinal Chemistry, Sanofi Research Division, Sanofi Winthrop Inc. Collegeville, Pennsylvania 19426-0900, USA.
J Med Chem. 1995 Sep 1;38(18):3586-92. doi: 10.1021/jm00018a018.
A series of permanently charged benzo[b]quinolizinium cations having lower lipophilicity than MK-801 or phencyclidine (PCP) were synthesized. Data relating agonist independent block of N-methyl-D-aspartic acid (NMDA) ion channels to log D are described. Closed channel access is predicted to result in a more noncompetitive profile of antagonism compared to selective open channel blockers, which are uncompetitive inhibitors. Reduced closed channel block may underlie the absence of PCP or MK-801-like behavioral side effects observed for benzo[b]-quinolizinium cations.
合成了一系列永久性带电的苯并[b]喹嗪鎓阳离子，其亲脂性低于MK-801或苯环己哌啶（PCP）。描述了与N-甲基-D-天冬氨酸（NMDA）离子通道的激动剂非依赖性阻断相关的log D数据。与选择性开放通道阻滞剂（非竞争性抑制剂）相比，预计封闭通道进入会导致更具非竞争性的拮抗作用。封闭通道阻断的减少可能是苯并[b]喹嗪鎓阳离子未观察到PCP或MK-801样行为副作用的原因。
