DRUGS USED IN THE TREATMENT OF
SCHIZOPHRENIA AND BIPOLAR DISORDER INHIBIT THE REPLICATION OF TOXOPLASMA
GONDII
Lorraine Jones-Brando, E. Fuller
Torrey, Robert Yolken
Schizophrenia Research
62(2003)237-244
ABSTRACT
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
b-galactosidase.
Inhibition by the drugs was determined by spectrophotemetric 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 the
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.