Concentration and distribution of thioridazine and metabolites in schizophrenic post-mortem brain tissue.

Thioridazine (THD) and its major metabolites, mesoridazine (MES), sulforidazine (SULF), and northioridazine (norTHD) accumulate at a predictable rate in human brain tissue after chronic medication. Although the concentration of THD is normally lower than or the same as its major metabolite, MES, in the plasma, it was found to be up to five times as concentrated in the brain tissue of treated patients. THD and its metabolites were evenly distributed throughout all regions of the brain in chronically medicated patients. Brain concentrations of THD were also compared with those of chlorpromazine (CPZ) when both drugs had been given at the same dose before death, and were shown to be up to 10 times more concentrated in brain at doses greater than 300 mg/day. Because some of the metabolites of THD are pharmacologically active, it is important to know how they accumulate in the brain in relation to the parent compound to understand how this drug mediates its clinical effect.