Old drug, new use

An antihistamine introduced in 1983 shows activity against malaria in mice. Researchers discovered the drug’s activity by screening a library of more than 2,000 existing drugs, a strategy that could reveal alternative uses for already approved drugs against other diseases.

David J. Sullivan Jr. of Johns Hopkins University in Baltimore and his colleagues assembled the library—the largest yet reported—from more than 1,900 U.S.–approved drugs and 750 others approved abroad or used in human trials. They then looked for compounds that stop the growth of Plasmodium falciparum, the parasite that causes malaria in people.

The screening identified the antihistamine astemizole, which was removed from American and European markets in the late 1990s because of potential damage to the heart.

Sullivan and his coworkers tested the drug in infected mice. Astemizole reduced the number of parasites by 80 percent in mice infected with a strain sensitive to chloroquine, one of the primary antimalaria drugs, and by 44 percent in mice with chloroquine-resistant parasites, the researchers report in the August Nature Chemical Biology.

The researchers plan to conduct more studies with astemizole. Meanwhile, they will expand their drug library to screen for activity against diseases that primarily affect the developing world, says Sullivan.

Such screens are “a really good idea,” comments Jonathan L. Vennerstrom, a medicinal chemist at the University of Nebraska in Omaha.

The identification of astemizole could be a starting point for a drug-development project, he adds. Chemical analogs of the drug might have better activity and less toxicity than astemizole itself, he says.

Aimee Cunningham is the biomedical writer. She has a master’s degree in science journalism from New York University.

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