Hopkins Scientists Find Antipsychotic Drug Has Anti-HIV Activity

June 10, 1997

Researchers at the Johns Hopkins Children's Center have discovered that some metabolites (breakdown products) of a common antipsychotic drug stop the replication of HIV in human cell cultures. The study was published in the May 13 issue of Schizophrenia Research.

Previous studies of antipsychotic have indicated that many of them possess anti-viral activity; for example, thorazine has been shown to slow the progression of AIDS in HIV-infected patients, and lithium can inhibit the replication of herpes simplex viruses.

"This is consistent with the possibility that viral infections may play a role in schizophrenia and other serious neuropsychiatric diseases,"says lead author Lorraine V. Jones-Brando, part of the Children's Center's Stanley Laboratory for the Study of Schizophrenia and Bipolar Disease.

Brando and colleagues studied clozapine, used in the treatment of approximately 58,000 schizophrenic patients each year, and nine of its metabolites, along with several other antipsychotic drugs.

Four clozapine metabolites inhibited the replication of three different strains of HIV at non-toxic concentrations. However, the effective concentrations of the metabolites were 6,000 times higher than an effective dose of AZT. Coupled with the shortage of information available on the levels of clozapine and its breakdown products in humans, the high concentrations necessary for anti-viral activity make clozapine an unlikely candidate for fighting HIV.

"Though the clozapine metabolites are unlikely to be useful for the treatment of HIV infection," says Jones-Brando, "it is possible they may inhibit the replication of other viruses at much lower concentrations." Preliminary findings by Jones-Brando and others indicate that some breakdown products of clozapine also inhibit Borna virus, which causes a fatal neurological disease.

Other researchers involved in the work were James L. Buthod and Louis E. Holland of IIT Research Institute, Chicago; Robert H. Yolken of the Stanley Laboratory at the Johns Hopkins Children's Center; and E. Fuller Torrey of the Twin Studies Unit at St. Elizabeths, Washington, DC.

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Johns Hopkins Medicine

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