Schizophrenia Research: in press
Drugs Used in the Treatment of Schizophrenia and
Bipolar Disorder Inhibit the Replication of Toxoplasma gondii
Lorraine Jones-Brando, E. Fuller Torrey, and Robert
Yolken
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 Toxoplasma gondii. Human fibroblasts
(HFF) were treated with test compounds and then exposed to Toxoplasma that has
been genetically modified to express cytoplasmic
ß-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 Toxoplasma gondii.