In a group of mice bearing experimentally induced
tumors, the protein binding of
mianserin in vitro was measured and compared with a control group. The
analgesic effect and the brain uptake of
drug was also compared with a control group after an intraperitoneal dose of
mianserin. The unbound percentage of
mianserin in the plasma of mice with experimental
cancer decreased with respect to control animals (5.20 +/- 0.12 vs 6.06 +/- 0.26; p<0.05) and alpha1-acid
glycoprotein (AAG) levels, measured as plasma mucoprotein concentrations, were significantly increased (p<0.05). The brain/plasma
drug concentration ratio of
mianserin decreased in mice with experimental
cancer when compared with control mice (1.11 +/- 0.03 vs 1.42 +/- 0.10; p<0.02). In both groups of mice, the
mianserin analgesic effect was evaluated by the hot plate test after intraperitoneal
drug administration. When the
analgesia response-dose curve (0-60 mg/kg) was studied, a significant decrease in the response in mice with experimental
cancer versus control mice was observed. These results suggest that resistance to the
mianserin analgesic response may occur in animals with
cancer disease. This resistance may be associated, in part, with an altered
plasma protein binding, but other mechanisms could be involved.