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Changes in the analgesic effects of mianserin associated with altered plasma protein binding in experimental cancer
I Torres1, E Suárez, J M Rodríguez-Sasiaín
1Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Abstract:
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.
Insights
Mice with cancer showed reduced mianserin analgesic effects and brain uptake. This resistance may stem from altered plasma protein binding, specifically increased alpha1-acid glycoprotein levels.
Area of Science:
- Pharmacology
- Oncology
- Neuroscience
Background:
- Mianserin is an antidepressant with analgesic properties.
- Cancer can alter drug pharmacokinetics and pharmacodynamics.
- Understanding these alterations is crucial for effective pain management in cancer patients.
Purpose of the Study:
- To investigate the effect of experimental cancer on mianserin's protein binding, brain uptake, and analgesic efficacy in mice.
- To explore potential mechanisms underlying altered mianserin response in cancer.
Main Methods:
- Experimental tumors were induced in mice.
- Mianserin's in vitro protein binding in plasma was measured.
- Analgesic effects were assessed using the hot plate test.
- Brain and plasma drug concentrations were determined.
Main Results:
- Mice with cancer exhibited decreased unbound mianserin percentage in plasma (5.20% vs 6.06%).
- Alpha1-acid glycoprotein (AAG) levels were significantly increased in tumor-bearing mice.
- The brain/plasma mianserin concentration ratio was lower in cancer mice (1.11 vs 1.42).
- A significant reduction in mianserin's analgesic response was observed in mice with cancer.
Conclusions:
- Cancer disease in mice is associated with resistance to mianserin's analgesic effects.
- Altered plasma protein binding, particularly increased AAG, may contribute to this resistance.
- Other uninvestigated mechanisms could also play a role in the observed resistance.
