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Changes in the analgesic effects of mianserin associated with altered plasma protein binding in experimental cancer.

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.
AuthorsI Torres, E Suárez, J M Rodríguez-Sasiaín, E Gomez, R Calvo
JournalResearch communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 89 Issue 3 Pg. 341-50 (Sep 1995) ISSN: 1078-0297 [Print] UNITED STATES
PMID8680802 (Publication Type: Journal Article)
Chemical References
  • Analgesics
  • Blood Proteins
  • Glycoproteins
  • Mucoproteins
  • Mianserin
Topics
  • Analgesics (pharmacology)
  • Animals
  • Binding, Competitive
  • Blood Proteins (drug effects)
  • Brain (metabolism)
  • Dose-Response Relationship, Drug
  • Glycoproteins (blood)
  • In Vitro Techniques
  • Mianserin (pharmacology)
  • Mice
  • Mice, Inbred C57BL
  • Mucoproteins (blood)
  • Neoplasms, Experimental

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