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Dizocilpine
Dizocilpine (INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. 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. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including 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 probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Olney's Lesions
Olney's lesions, also known as NMDA receptor antagonist neurotoxicity (NAN), are a form of potential brain damage due to drugs that have been studied experimentally and have produced neuronal damage, yet are administered by doctors to humans in the settings of pharmacotherapy and of anesthesia. They are named after John Olney, who conducted a study in 1989 to investigate neurotoxicity caused by PCP and related drugs. They are important for two reasons. Firstly, NMDA receptor antagonists are physician-prescribed drugs for therapeutic treatment of human diseases such as memantine for Alzheimer's disease and amantadine for Parkinson's disease, and also occur as street drugs that are taken recreationally. Secondly in the field of anesthesiology, the dissociative anesthesia of many general anesthetics is due to NMDA receptor antagonist properties. Because the neuronal vacuolation of Olney's lesions evolves into neuronal necrosis or death of neurons, it is important to determine whether O ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
