N-Methyl-D-aspartic acid receptors (NMDAR) are a family of neurotransmitter receptors that mediate the action of excitatory amino acids in signal transduction. (+)-MK-801 maleate is a potent, selective, and non-competitive NMDAR antagonist with Kd values of 37.6, 37.2, 40.0 and 56.2 nM in rat brain membranes from hippocampus, cortex, striatum and medulla-pons, respectively[1]. In rat hippocampal tissue, MK-801 inhibited [3H]TCP binding, NMDA-induced [3H]norepinephrine (NE) release, and [3H]NE uptake with IC50 values of 9, 20, and 2030 nM, respectively[2]. In cultured cortical neurons, 10 μM MK-801 blocked NMDA-stimulated current with a time constant of around 11 seconds. MK-801 at 2 μM blocked NMDA-induced unitary currents in outside-out patches[3]. The activation of microglia induced by LPS (100 mg/mL) was inhibited by 50 – 500 μM MK-801 at a dose-dependent manner. MK-801 from 50 – 500 μM also decreased Tat72-stimulated (200 ng/mL) increase in Cox-2 protein expression in BV-2 cells. In mice received i.p. administration of METH, pre-treatment of MK-801 (1 mg/kg) 15 min prior to METH injection resulted in 55% reduction of DA depletion. The effect of METH on microglia activation in the striatum of mice was also significantly attenuated by the same treatment of MK-801[4].
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