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

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Abstract
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 < 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 < 0·05) and seromucoid levels were significantly increased (P < 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 < 0·02), suggesting that the decrease in analgesia was secondary to a decrease in drug delivery to the brain because of increased protein binding.