Antihistamine Identified as Potential Antimalarial Drug

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The allergy medication astemizole could have another life as a potential treatment for malaria, according to a study conducted by researchers from the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University School of Medicine. The study, largely funded by the Johns Hopkins Malaria Research Institute (MRI), determined that in a test tube the antihistamine killed the parasite, Plasmodium falciparum, which causes malaria in humans, including parasite strains that were resistant to traditional malaria therapies. The drug was also shown to be effective in mouse models. The findings are published in the July 2, 2006, advanced online edition of Nature Chemical Biology.

“Time and money are major roadblocks when it comes to developing new drugs for the treatment of neglected diseases like malaria,” said senior study author David Sullivan, MD, an associate professor with MRI and the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology. “Astemizole is promising as an antimalarial, but still needs to be evaluated for effectiveness as an antimalarial in humans.”

For the study, Sullivan and colleagues Curtis Chong and Jun Liu of the Johns Hopkins School of Medicine’s Department of Pharmacology first assembled the Johns Hopkins Clinical Compound Library, which is a collection of 2,687 drugs. Seventy percent of the compounds are approved by the U.S. Food and Drug Administration, while the remaining 30 percent are approved by regulatory agencies in other countries. The researchers screened the drugs for their effectiveness in killing the malaria-causing parasite and found that astemizole was one of the more promising.

The researchers then gave astemizole, along with the drug’s major human metabolite, desmethylastemizol, to mice infected with Plasmodium. They measured 80 percent reduction in parasite counts with moderate doses of drug in chloroquine-sensitive mice and 40 percent reductions in chloroquine-resistant mice. Higher doses completely eliminated Plasmodium infection.

Astemizole was voluntarily withdrawn from the U.S. and European markets in 1999 after 15 years of use when sales became sluggish after warnings about the drug’s safety and the introduction of newer antihistamines. The drug was reported to cause rare, but life-threatening heart arrhythmias when patients took an overdose or with drugs that affected its metabolism. However, arrhythmias are also reported with existing malaria drugs and other antihistamines now sold over the counter. Astemizole is currently still used in 30 countries, including Cambodia, Thailand and Vietnam where malaria is endemic.

Human studies are planned to evaluate the effectiveness of astemizole directly in asymptomatic malaria patients, a process that will be accelerated by the fact that the medication has been through an approval process. The researchers hope to next validate this new drug class for use in combination with existing malaria drugs like artemisinin or the quinolines.

The Johns Hopkins Clinical Compound Library will now be available to screen existing drugs for new uses for diseases affecting the developing world. “This line of research can be applied to many neglected diseases,” said Chong, the lead author of the study.

Editors Note: David Sullivan will be available for interviews June 29 and June 30. He will have only limited availablity July 1 through July 9.

“A clinical drug library screen identifies astemizole as an antimalarial agent” was written Curtis R. Chong, Xiaocum Chen, Lirong Shi, Jun O Liu and David J. Sullivan Jr.

The research was supported by the Johns Hopkins Malaria Research Institute, the Johns Hopkins University Fund for Medical Discovery and Department of Pharmacology, and the Keck Foundation.

Johns Hopkins Bloomberg School of Public Health

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