Sea worms and plants spur new drugs.

Earth's seas and forests, some of nature's most productive chemical laboratories, continue to brew concoctions that hold promise as human medicines. By subtly modifying two obscure natural molecules -- one from an ocean creature and one from a plant -- scientists are developing potential new treatments for Alzheimer's disease, a degenerative brain condition that affects an estimated 5 million Americans over the age of 65.

William R. Kem, a chemist at the University of Florida, Gainesville, and his colleagues have synthesized from a neurotoxin found in marine worms a compound that ameliorates some symptoms of Alzheimer's disease. The compound, GTS-21, "acts in a way totally different from previously investigated drugs," Kem said this week at a meeting of the American Chemical Society in Anaheim, Calif. "It stimulates a particular type of site in the brain called the alpha 7-type nicotine receptor."

The brain has several varieties of nicotine receptors, which affect autonomic nervous system functions controlling blood circulation, digestion, and skeletal muscles. However, if scientists can stimulate the alpha 7 receptors without disturbing the other nicotine receptors, they may be able to enhance cognitive abilities without causing undesirable side effects.

Those effects, including high blood pressure, anxiety, and disturbance of heart rhythm, make nicotine itself an unsafe treatment for Alzheimer's patients.

Kem and his colleagues derived GTS-21 from anabaseine, a toxin used by nemertine worms to paralyze prey and deter predators. After synthesizing and testing more than 100 derivatives of the toxin over 8 years, Kem's team concluded that GTS-21 has the greatest potential as a drug for treating Alzheimer's disease in human beings.

As Alzheimer's progresses, nicotine receptors in the brain gradually disappear; half of them may have vanished by the time a patient dies. The GTS-21 compound aims to stimulate the surviving nicotine receptors and delay the onset of debilitating symptoms.

Although the drug does not cure Alzheimer's disease or repair underlying nerve damage, it does lessen neurological symptoms in laboratory animals. Tests of GTS-21 in rats showed boosts in memory and a slowing of nerve cell degeneration, Kem says. An animal trial to measure cognitive abilities found that old rabbits exposed to the new compound could learn almost as rapidly as young rabbits, reports Diana Woodruff-Pak at Temple University in Philadelphia.

In humans, warding off the debilitating and life-threatening symptoms of Alzheimer's disease may help patients and their families cope with the condition's devastating effects. Delaying hospitalization by 6 months to a year could save billions of dollars in health care costs, Kem says. Clinical trials of GTS-21 will begin in late 1995.

Two other molecules that may help Alzheimer's patients come from the Caucasian snowdrop, a member of the Amaryllidoidae plant family. Raymond W. Kosley, a chemist at Hoechst-Roussel Pharmaceuticals in Somerville, N.J., and his coworkers derived the two compounds, P11012 and P11149, from galanthamine, an alkaloid substance found in the plant.

Since Alzheimer's patients tend to suffer from low concentrations of the neurotransmitter acetylcholine, the researchers looked for a compound that could diminish breakdown of this substance in the nervous system.

Both P11012 and P11149 achieved that goal in animals, mimicking the positive effects of the drug Tacrine, currently used to treat people with Alzheimer's disease. Users of Tacrine, however, can suffer liver damage. In Europe, some people with the neuromuscular disease myasthenia gravis are taking the new compounds, without reported liver damage.

In the United States, clinical trials of the new galanthamine derivatives may begin within a year, Kosley says.