Clozapine concentrations in brain regions: relationship to dopamine metabolite increase

Levels of clozapine in rat striatum and tuberculum olfactorium were quantitated by a gas chromatographic technique. The relationship of the increase in 3,4-dihydroxyphenylacetic acid (DOPAC) in these regions produced by clozapine to the concentration of clozapine was explored. One hour after 10, 20 or 40 mg/kg clozapine i.p. the concentration of drug increased in proportion to the dose and at each dose was similar in striatum and T.O. The percent increase in DOPAC in both areas was related to the clozapine concentration in a typical dose--response manner and was greater in the striatum than the T.O. A relatively high concentration of clozapine (40 micron) was required to produce a half-maximal elevation of DOPAC. Striatal clozapine levels were similar in acutely and chronically treated animals. The concentrations of clozapine in striatum and T.O. reflect the dose injected and do not account for its atypical properties.