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MK-801 is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. It was discovered in 1981 as an anaesthetic, but it also has been studied for other purposes, including its ability to reverse memory deficits and depression. MK-801 is not water soluble, so it cannot penetrate the blood-brain barrier and enter the brain. However, it can be administered intravenously to reach the peripheral nervous system. The drug binds reversibly to NMDA receptors on neurons throughout the central nervous system and prevents them from opening in response to glutamate. This inhibits long-term potentiation (LTP), a process that strengthens connections between nerve cells in order to make memories last longer. Long-term depression (LTD) is another type of synaptic plasticity that may underlie some types of memory loss or other cognitive deficits. The effects of MK-801 on LTD are unknown, but it has been shown to have antidepressant properties in rats with brain lesions that
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