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Mapping brain disorder therapeutics at work

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Cold Spring Harbor Laboratory Professor Hiro Furukawa is exploring how different drugs bind to and inhibit the NMDA receptor in the brain. The receptor is known to play an important role in brain disorders like Alzheimer’s and depression. Furukawa and his team built high-resolution, 3D atomic maps to closely examine how three drugs bind to NMDA and affect the receptor’s functions.

The team looked at two FDA-approved drugs called memantine and ketamine and a recreational drug known as PCP. All three drugs are known to inhibit the receptor but could cause different levels of side effects like psychosis. The researchers found that each drug binds to a similar area on the NMDA receptor, but in different positions—which leads to different effects.

Using their high-resolution atomic maps, Furukawa and his colleagues found that PCP bound the best and the longest to the NMDA receptor, followed by ketamine and memantine. PCP also had the greatest impact on its function. Understanding why the drugs bound differently may help develop brain disorder therapeutics with more efficient binding and less side effects.

Read the related story: Mapping out new routes to treat brain disorders