Ca[2+] inhibits the association of memantine with N-methyl-D-aspartate (NMDA) receptor-gated cannels

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  • Fujimoto Masafumi
    Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Science, Chiba Institute of Science
  • Iida Hirokazu
    Laboratory of Organic Chemistry, Faculty of Pharmaceutical Science, Chiba Institute of Science
  • Homma Tomoo
    Department of Environmental System Science, Faculty of Risk and Crisis Management, Chiba Institute of Science
  • Kimura Ikuo
    Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Science, Chiba Institute of Science
  • Mori Masahiro
    Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Science, Chiba Institute of Science
  • Hamana Hiroshi
    Laboratory of Organic Chemistry, Faculty of Pharmaceutical Science, Chiba Institute of Science

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  • Ca2+ Inhibits the Association of Memantine with N-Methyl-D-aspartate (NMDA) Receptor-Gated Ion Channels

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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 [3H]MK-801 binding to crude synaptic membranes of rat forebrains in the absence or presence of Ca2+. Ca2+ decreased the potency of memantine to inhibit [3H]MK-801 binding. The effect of Ca2+ was apparently competitive with memantine and was not annulled by the addition of Mg2+. Ca2+ slightly enhanced [3H]MK-801 binding, but showed no effect on the displacement of [3H]MK-801 binding by MK-801. The Ca2+-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.

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