Potential Drug to Improve Memory

WASHINGTON, D.C.--A pill that boosts memory power may not be as far-fetched as it sounds. Ampakines, a class of compounds that make nerve cells more sensitive to the amino acid glutamate, may improve some kinds of short-term memory, researchers reported at the Society for Neuroscience's annual meeting here yesterday.

In a pilot study carried out in Berlin, Gary Lynch of the University of California, Irvine, and his colleagues at Cortex Pharmaceuticals in Irvine had about two dozen subjects listen to a sequence of 10 nonsense syllables, then try to recall the syllables 5 minutes later. Healthy 20- to 25-year-olds remembered about half the syllables, while normal 65- to 73-year-olds typically remembered only one. But ampakines provided a real boost: When elderly subjects were given ampakines before the test, they remembered on average three syllables. A second study suggests that the compounds may improve the memories of younger people as well.

Ampakines appear to flex their memory-enhancing powers by increasing brain cell uptake of glutamate, a neurotransmitter. Glutamate triggers receptor proteins to open an ion channel in a neuron's membrane, which allows positively charged ions to flow into the cell. Ampakines influence a certain kind of glutamate receptor, called the AMPA receptor, to keep the ion channel open a bit longer than normal. This essentially gets more bang for the buck--more nerve cell excitation from each glutamate molecule.

The researchers are proceeding carefully in human trials and using low doses of the drugs, because animal experiments have shown that overactivation of excitatory glutamate receptors with ampakines can lead to seizures. But no seizures have been observed in the human subjects so far, and Lynch and his colleagues are planning a small U.S. trial in patients with Alzheimer's disease. There's no reason to believe that ampakines would slow the nerve-cell death seen in Alzheimer's disease, says Dennis Selkoe, an expert on the disease at Harvard Medical School in Boston. Rather, Selkoe says, ampakines may someday become part of "an array of therapeutics" in which these compounds make the most of the neurons that remain.