Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1

Lorraine V. Jones-Brando, James L. Buthod, Louis E. Holland, Robert H. Yolken, E. Fuller Torrey

Research output: Contribution to journalArticle

Abstract

Schizophrenia is a serious and often debilitating neuropsychiatric disease of worldwide importance. Current therapy relies on the use of typical antipsychotic medications, which specifically inhibit binding of ligand at the D2 dopamine receptor, and atypical medications which display little activity for this receptor interaction. While atypical antipsychotic agents have been shown to variably inhibit other neuroreceptor-ligand interactions, the exact mechanisms for the therapeutic efficacy of these medications have not been completely defined. Clozapine, an atypical antipsychotic, and nine of its metabolites were studied in vitro for possible antiviral activity against a model of a human neurotropic virus, human immunodeficiency virus type 1 (HIV-1). In an assay for inhibition of virus-induced cytopathic effect (CPE) two metabolites demonstrated antiviral activity (ID50=37-85 μg/ml) (119-289 μM), while other atypical or novel antipsychotics as well as typical medications had no effect. Based on an ELISA, four chemically similar metabolites inhibited the production of p24, the major internal antigen of HIV (ID50 = 11.6 15.7 μg/ml) (38-51 μM). These data suggest that the therapeutic efficacy of some antipsychotics may be due in part to an ability to inhibit viral replication. Antiviral agents may prove to be effective adjuncts in the treatment of schizophrenia.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalSchizophrenia Research
Volume25
Issue number1
DOIs
StatePublished - May 3 1997

Keywords

  • Antipsychotic
  • Antiviral
  • Schizophrenia
  • Virus

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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