Class acts from new pesticides: chemicals have little effect on mammals.

Insects, be warned. Research on three continents has turned up two new classes of selective pesticides that immobilize and eventually kill many insect species by interfering with a cell receptor unique to the insects. The novel chemicals could potentially prevent infestations of crops while posing minimal danger to noninsects.

"Both classes of chemicals act at the ryanodine receptor" making them the first synthetic molecules to demonstrate this insect-imperiling behavior, says physiologist Daniel Cordova of DuPont Crop Protection in Newark, Del. By regulating how calcium moves within animal cells, that receptor plays an essential role in processes such as muscle contraction.

Ryanodine binds to its receptor, says Cordova, "acting much like a doorstop, in that it locks the channel in a partially open state, resulting in calcium depletion" within cells and loss of muscle control. Vertebrates have two or three forms of the receptor, none of which is identical to the single form present in insects.

"For over 50 years, scientists have postulated that [the receptor] would be a good target" for insecticides, Cordova says. But ryanodine itself, a natural chemical defense that plants muster to ward off insects, is too complex to synthesize economically, he says. Other previously known triggers of the ryanodine receptor, including caffeine, have negligible effects except at extremely high concentrations.

Now, three research groups--Cordova's DuPont team and two teams based in Germany and Japan--have produced chemicals that mimic ryanodine in insect cells. The three teams described their research on Aug. 28 at a meeting in Washington, D.C., of the American Chemical Society.

During the 1990s, while attempting to create new weed killers, scientists at Nihon Nohyaku Co. in Osaka, Japan, developed the first compounds known as benzenedicarboxamides or phthalic acid diamides. The chemicals weren't effective as herbicides, but in some insects they caused distinctive symptoms, including muscle contractions.

Kenji Tsubata and his Nihon Nohyaku colleagues recently developed a particularly potent benzenediearboxamide called flubendiamide. At various concentrations, the compound is lethal to more than half-a-dozen species of destructive insects, including some that are resistant to other insecticides.

Even at concentrations at least 100-fold those sufficient to poison these pests, flubendiamide doesn't appear to harm rats, honeybees, spiders, or any of several beneficial predatory-insect species, the Japanese researchers reported. They noted, however, that the compound can kill silkworms.

Regulatory approval of flubendiamide is pending in Japan but not yet imminent in the United States or Europe, says Peter Lummen of Bayer CropScience in Monheim, Germany.

For their part, Lummen and his Bayer colleagues are studying whether flubendiamide interacts with any of three mammalian ryanodine receptors. In tests so far, the chemical appears to be inactive against at least two of the receptors.

In separate research, DuPont chemists invented compounds called anthranilic diamides that bind 500 to 2,000 times more readily to the insect receptor than to the mammalian receptors. These chemicals cause rapid, progressive, and often lethal muscle paralysis in a range of insects, Cordova reported.

The complementary nature of the recent findings, Lummen says, hints strongly "that we are on the right track" toward a safe new class of pesticides.