An NMDA receptor antagonist
(+)-MK 801 is a potent antagonist of NMDA with Ki value of 30.5nM [1].
MK 801 is a potent anticonvulsant exhibits both anxiolytic and sympathomimetic properties. It is found to be a noncompetitive antagonist of NMDA. MK 801 can penetrate into the central nervous system. In the in vitro assay, MK 801 binds to rat cerebral cortical membrane with high affinity in a saturable manner. This binding is reversible even when the concentration of MK 801 is up to 100μM. It is also found that the binding shows a regional specificity. Most of these binding sites are located in the hippocampus. In rat cortical-slice preparations, MK 801 causes a potent blockade of depolarizing responses to NMDA with a high selectivity. This effect is persistent. The blockade can also cause a suppression of the epileptiform activity induced by tetrodotoxin or other neurotoxin [1].
（+）-MK 801是NMDA的有效拮抗剂，Ki值为30.5nM[1]。
MK 801是一种强效抗惊厥药，具有抗焦虑和拟交感神经的特性。发现它是NMDA的非竞争性拮抗剂。MK 801可穿透中枢神经系统。在体外测定中，MK 801以可饱和的方式以高亲和力结合大鼠大脑皮层膜。即使MK 801的浓度高达100μM，这种结合也是可逆的。研究还发现，这种结合具有区域特异性。这些结合位点大多位于海马体。在大鼠皮层切片制剂中，MK 801以高选择性引起对NMDA去极化反应的有效阻断。这种影响是持久的。阻断也可抑制河豚毒素或其他神经毒素诱导的癫痫样活动[1]。
参考文献:
[1] Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL . 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.
| Cell experiment [1]: | |
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Cell lines |
Primary mixed neuronal/glial cultures from fetal rat brains. |
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Preparation method |
The solubility of this compound in DMSO is >16.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM for 30 minutes |
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Applications |
NMDA induced apoptosis in mixed neuronal/glial cell cultures. In the presence of a mild excitotoxic insult, this investigation showed an attenuation of apoptotic cell death by MK 801. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6; BALB/c mice |
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Dosage form |
s.c. or i.p., 0.1 mg kg(-1) |
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Application |
MK 801 in the chronically C57BL/6 chronic stress group that prevented weight gain deficit. For the C57BL/6 strain chronic MK 801 produced an alteration of the fur state. In the CA1 layer of chronically stressed C57BL/6 mice, MK 801 induced an increase of VGLUT1 immunoreactivity. For the BALB/c group, MK 801 enhanced BDNF mRNA in the chronic stress group in the DG. In the chronically stressed BALB/c mice, MK 801 prevented stressed induced VGLUT3 immunoreactivity up-regulation in the CA3 layer. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Wise-Faberowski L,Pearlstein RD,Warner DS., et al. NMDA-induced apoptosis in mixed neuronal/glial cortical cell cultures: the effects of isoflurane and dizocilpine. J Neurosurg Anesthesiol.2006 Oct;18(4):240-6. [2] .Farley S, Dumas S, El Mestikawy S ., et al. Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: effects of fluoxetine and MK-801. Neuropharmacology. 2012 Jan;62(1):503-17. |
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