Changes in amitriptyline distribution in rat brain during a 14-day continuous infusion

The amitriptyline (ATL) distribution in 12 rat brain regions was examined during 2-, 7- and 14-day continuous ATL infusion, starting with 18 mg/kg/day on the first day. The concentration of nortriptyline, a demethylated metabolite of ATL, in brain and serum was very low in comparison with ATL. The brain/serum concentration ratio of ATL and absolute ATL concentration in the brain were lower on the 2nd day than on the other 2 days. On the other hand, the ATL serum level on the 2nd day was higher than on the other 2 days. The ATL distribution in brain was heterogeneous on each of the three days and there were changes with time in its distribution in two brain portions, the anterior basal ganglia and the medulla oblongata + pons.