钙离子抑制美金刚与N-甲基-D-天冬氨酸（NMDA）受体门控离子通道的结合。

Ca2+ inhibits the association of memantine with N-methyl-D-aspartate (NMDA) receptor-gated ion channels.

作者信息

Fujimoto Masafumi, Iida Hirokazu, Homma Tomoo, Kimura Ikuo, Mori Masahiro, Hamana Hiroshi

机构信息

Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Science, Chiba Institute of Science, Coshi, Chiba, Japan.

出版信息

Biol Pharm Bull. 2008 Sep;31(9):1813-5. doi: 10.1248/bpb.31.1813.

DOI:10.1248/bpb.31.1813

PMID:18758084

Abstract

We examined the effect of 1-amino-3,5-dimethyladamantane (memantine) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) on the inhibition of [(3)H]MK-801 binding to crude synaptic membranes of rat forebrains in the absence or presence of Ca(2+). Ca(2+) decreased the potency of memantine to inhibit [(3)H]MK-801 binding. The effect of Ca(2+) was apparently competitive with memantine and was not annulled by the addition of Mg(2+). Ca(2+) slightly enhanced [(3)H]MK-801 binding, but showed no effect on the displacement of [(3)H]MK-801 binding by MK-801. The Ca(2+)-sensitive interaction of memantine with N-methyl-D-aspartate (NMDA) receptor-gated ion channels may provide a clue to understanding its voltage-dependent and clinically tolerated character.

摘要

我们研究了1-氨基-3,5-二甲基金刚烷（美金刚）和（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（MK-801）在有无Ca(2+)存在的情况下对[(3)H]MK-801与大鼠前脑粗突触膜结合的抑制作用。Ca(2+)降低了美金刚抑制[(3)H]MK-801结合的效力。Ca(2+)的作用显然与美金刚具有竞争性，并且不会因添加Mg(2+)而消除。Ca(2+)略微增强了[(3)H]MK-801的结合，但对MK-801取代[(3)H]MK-801结合没有影响。美金刚与N-甲基-D-天冬氨酸（NMDA）受体门控离子通道的Ca(2+)敏感相互作用可能为理解其电压依赖性和临床耐受性特征提供线索。