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出典:『Wikipedia』 (2011/06/14 09:27 UTC 版)

英語による解説

引用

Dizocilpine (INN), also known as MK-801, is a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. MK-801 binds inside the ion channel of the receptor at the PCP binding site and thus prevents the flow of ions, including an influx of calcium (Ca²⁺), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and likely has dissociative anesthetic properties, but it is not used clinically for this purpose due to the discovery of brain lesions, called Olney's lesions (see below), in test rats. MK-801 is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It also inhibited the induction of long term potentiation. Instead, the NMDA receptor pore-blocker ketamine is used as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used non-competitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.