EFFLUX OF CHLORPROMAZINE AND TRIFLUOPERAZINE FROM THE RAT BRAIN

¹ Departments of Pharmacology and Neurology, College of Physicians and Surgeons of Columbia University, New York, New York; Smith Kline and French Laboratories, Philadelphia, Pennsylvania

Chlorpromazine (CPZ) and trifluoperazine (TFP) attained equal concentrations in rat brain one hour after an i.v. injection of 4.2 µmol/kg, and both declined at similar rates. After 42 µmol/kg, both drugs again attained equal concentrations in brain at one hour, but only TFP declined as it did after the low dose. CPZ declined rapidly at first and then more slowly. The hypothermic and hypotensive properties of CPZ were not responsible for the altered kinetics. Administering CPZ sulfoxide, 42 µmol/kg, prior to a low dose of CPZ or TFP slowed their efflux from brain. CPZ sulfoxide concentrations in plasma were always higher and declined slower than TFP sulfoxide when the parent compounds were administered in equal doses. Moreover, CPZ sulfoxide inhibited the metabolism of CPZ in a liver homogenate. CPZ metabolites probably accumulated after the high dose and retarded further CPZ metabolism, thereby delaying its disappearance from brain.