Influence of changes in protein binding on the central activity of antidepressants.

The central effect (expressed as analgesic response), protein binding and brain uptake of mianserin were measured in mice receiving drug intraperitoneally. A significant decrease of the central effect of mianserin (30 mg kg-1) was seen in mice with experimental inflammation when compared with control animals (reaction time (s) = 12.12 +/- 1.22 vs 25.56 +/- 2.92; P less than 0.001) and the dose-analgesia response curve (10-60 mg kg-1) was significantly shifted to the right in mice with inflammation. In serum of mice with inflammation, unbound concentration of mianserin was decreased from 19.37 +/- 0.73 to 17.83 +/- 0.30% (P less than 0.05) and seromucoid levels were significantly increased (P less than 0.001). Following the intraperitoneal administration of 30 mg kg-1 of mianserin, brain uptake decreased in diseased mice when compared with control animals (P less than 0.02), suggesting that the decrease in analgesia was secondary to a decrease in drug delivery to the brain because of increased protein binding.