(+)-MK 801 (Maleate) is a potent, selective and non-competitive NMDA receptor antagonist with K_d of 37.2 nM in rat brain membranes.

Ki: 30.5 nM

[³H]MK-801 labels high-affinity binding sites in rat cerebral cortical membranes in a saturable manner. MK-801 produces a potent blockade of depolarizing responses to NMDA in rat cerebral cortical slices. The only compounds that are able to compete for [³H]MK-801 binding sites are substances known to block the responses of excitatory amino acids mediated by the NMDA receptor subtype^[1]. MK-801 inhibits N-methyl-D-aspartate-induced [³H]norepinephrine (NE) release and [³H]TCP binding in the hippocampus with IC₅₀ of 20 nM and 9 nM, respectively^[2]. MK-801 causes a progressive, long-lasting blockade of current induced by NMDA. Mg²⁺ (10 mM) prevents MK-801 from blocking the N-Me-D-Asp-induced current, even when MK-801 is applied for a long time in the presence of NMDA. MK-801 is also effective at blocking NMDA-activated single-channel activity in outside-out patches^[3]. MK-801 (< 500="" μm)="" prevents="" lps-induced="" activation="" of="" microglia="" in="" a="" concentration-dependent="" manner="" with="" increased="" cox-2="" protein="" expression="" in="" bv-2="" cells.="" mk-801="">< 500="" μm)="" reduces="" microglial="" tnf-α="" output="" with="">₅₀ of 400 μM in BV-2 cells^[4]. 

Treatment of mice with MK-801 (1 mg/kg) before each METH injection reduces the extent of DA depletion by 55% in striatal of mice. MK-801 (1 mg/kg) attenuates the effects of METH on microglial activation in striatal of mice^[4]. MK-801 (0.05 mg/kg or 0.2 mg/kg, i.p.) in rats just prior to reactivation of the cocaine-associated memory in the CPP context attenuates subsequent cocaine-primed reinstatement, while no disruption occurres in rats that do not receive reactivation in the CPP context. MK-801 (0.2 mg/kg, i.p.) prior to two reactivation sessions in the home cage does not suppress subsequent cocaine-primed reinstatement^[5]. 

• [1]. Wong EH, et al. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.

  [2]. Snell LD, et al. Comparison of the effects of MK-801 and phencyclidine on catecholamine uptake and NMDA-induced norepinephrine release. Eur J Pharmacol. 1988 Jan 12;145(2):223-6.

  [3]. Huettner JE, et al. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11.

  [4]. Thomas DM, et al. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.

  [5]. Brown TE, et al. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem. 2008 Dec 2;15(12):857-65.

  [6]. Jiang L, et al. Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-methyl-D-aspartate receptor activation. Neuroreport. 2017 May 24;28(8):444-450.

Cerebral cortices from male Sprague-Dawley rats (200-300 g) are homogenized in 9 volumes of ice-cold 0.32mol/Lsucrose by nine strokes with a Teflon/glass homogenizer at 500 rpm. The homogenate is centrifuged for 10 min at 1×10³ g, and the supernatant is recentrifuged at 1×10⁴ g for 20 min at 4°C. The pellet is suspended in assay buffer (118 mM NaCl/4.7 mM KCl/1.2mM MgSO₄/5 mM NaHCO₃/20 mM Hepes/1.2 mM KH₂PO₄/2.5 mM CaCl₂/11 mM glucose, pH 7.4) and incubated at 23°C for 20 min prior to final centrifugation at 1×10³ g for 20 min at 4°C. The pellet is resuspended in assay buffer (70 mL per gram of original tissue). Binding of [³H]MK-801 is measured by incubating 750 μL duplicate aliquots of this crude membrane suspension (=0.75 mg of protein) with 100 μL of buffer containing displacer or of buffer alone (total binding), 100 μL of 50 nM [³H]MK-801, and 50 μL of buffer for 60 min at 23°C. Nonspecific binding is defined by 100 μM (final concentration) unlabeled MK-801. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

MK-801 is formulated in saline.

Animals are given saline or MK-801 followed by cocaine 30 min later in the home cage instead of in the CPP apparatus for the two days of “reactivation.” This is done to determine whether reactivation of the memory for the cocaine-associated context by cocaine in the CPP context is necessary for the ability of MK-801 to disrupt reconsolidation. Animals undergo preconditioning, conditioning, testing, and extinction but animals are injected with saline or MK-801 (0.20 mg/kg, i.p.) 30 min prior to a cocaine injection (10 mg/kg, i.p.) in the home cage. Animals remain in the home cages, and the next day, the procedure from the first day of reactivation is repeated. The following day, animals are tested for cocaine-primed reinstatement in their CPP box without any prior microinjection of saline or MK-801. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Wong EH, et al. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.

  [2]. Snell LD, et al. Comparison of the effects of MK-801 and phencyclidine on catecholamine uptake and NMDA-induced norepinephrine release. Eur J Pharmacol. 1988 Jan 12;145(2):223-6.

  [3]. Huettner JE, et al. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11.

  [4]. Thomas DM, et al. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.

  [5]. Brown TE, et al. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem. 2008 Dec 2;15(12):857-65.

  [6]. Jiang L, et al. Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-methyl-D-aspartate receptor activation. Neuroreport. 2017 May 24;28(8):444-450.

337.37

C₂₀H₁₉NO₄

77086-22-7

Room temperature in continental US; may vary elsewhere

10 mM in DMSO; Ethanol：6 mg/mL; H₂O：< 0.6="">

MK-801 is dissolved in 1% dimethyl sulfoxide and diluted with preservative-free normal saline at a concentration of 2 μg/μL^[6].

* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

• [1]. Wong EH, et al. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.

  [2]. Snell LD, et al. Comparison of the effects of MK-801 and phencyclidine on catecholamine uptake and NMDA-induced norepinephrine release. Eur J Pharmacol. 1988 Jan 12;145(2):223-6.

  [3]. Huettner JE, et al. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11.

  [4]. Thomas DM, et al. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.

  [5]. Brown TE, et al. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem. 2008 Dec 2;15(12):857-65.

  [6]. Jiang L, et al. Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-methyl-D-aspartate receptor activation. Neuroreport. 2017 May 24;28(8):444-450.