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A Chance to Help Brain Disorders

Medicine: An experimental drug shows promise against Alzheimer's and schizophrenia.

May 17, 1999|JAMIE TALAN

An experimental memory drug being tested for Alzheimer's disease may give the damaged brain what it needs--better regulation of the brain chemical glutamate--and researchers believe it may improve a number of conditions, including schizophrenia and movement disorders.

The drugs, called ampakines, work where there's a demand for glutamate, the brain's major excitatory response neurochemical. Ampakines intensify the brain transmitter AMPA-glutamate, which is needed for neurons to communicate with one another. These receptors are more abundant in higher functioning brain regions.

Gary Lynch, a scientist at UC Irvine, suspects that ampakines rebuild damaged glutamate networks in the brain. After a stroke, for instance, glutamate receptors become damaged.

"As you lose these connections, bit by bit, the picture becomes fragmented, and it can't come into focus," Lynch explained. "Ampakines provide a boost to the remaining connections to give the brain a larger signal. The result is that the picture comes into focus again."

The latest study, presented last week by Lynch at the Society for Biological Psychiatry meeting in Washington, D.C., suggests that ampakines might also be used to treat movement disorders.

Lynch's research involved rodents with a specific brain lesion. The foot on the same side as the lesion would not stop moving in these animals. But when given ampakines, the animals' movement stopped. Their brains showed that the experimental medicine more than doubled the electrical activity in the area of the brain that controls the movement of the leg.

"It's really impressive," Lynch said. "We're thrilled that it worked so beautifully."

Glutamate is triggered during learning and memory, and thus ampakines became a natural compound to test against Alzheimer's. Ampakines given to old rats helped them perform like young rats. Studies in healthy humans found similar mental improvements.

More recently, evidence has been mounting that glutamate is the deficient chemical that underlies schizophrenia. People with schizophrenia often have many problems thinking clearly and focusing attention. For decades, researchers had focused on another brain chemical, dopamine, simply because the drugs used to treat delusions and hallucinations work on the brain's dopamine receptors.

There are no drugs on the market that regulate glutamate, and several experimental compounds have been dropped because of toxicity problems. Too much glutamate can kill brain cells. But ampakines so far have not exhibited this problem.

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