Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii.
The exact mechanisms of action of some antipsychotics and mood stabilizers have not been elucidated. Response to these medications can vary among individuals. Recent studies indicate that infection with the parasite Toxoplasma gondii may contribute to the symptoms of schizophrenia in some individuals. We investigated commonly used antipsychotic and mood stabilizing medications for their ability to inhibit the replication of this organism. We employed a system for testing compounds for in vitro activity against T. gondii. Human fibroblasts (HFF) were treated with test compounds and then exposed to Toxoplasma that has been genetically modified to express cytoplasmic beta-galactosidase. Inhibition by the drugs was determined by spectrophotometric analysis of colorimetric reactions. We tested 12 neuroleptic compounds and found that of these, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro. Valproic acid inhibited the parasite at a concentration below that found in the cerebrospinal fluid and blood of individuals being treated with this medication and displayed synergistic activity with haloperidol and with trimethoprim, an antibiotic commonly used to treat Toxoplasma infections.Several medications used to treat schizophrenia and bipolar disorder have the ability to inhibit the in vitro replication of T. gondii.
Jones-Brando
Lorraine
L
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Blalock 1149, Baltimore, MD 21287-4933, USA. lbrando@jhmi.edu
Torrey
E Fuller
EF
Yolken
Robert
R
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002462:Cell Membrane / Q000201:enzymology / Q000469:parasitology; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D012559:Schizophrenia / Q000188:drug therapy*; D013053:Spectrophotometry; D014122:Toxoplasma / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D014150:Antipsychotic Agents; D001616:beta-Galactosidase