Schizophrenia Research



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



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.