Novel anti-inflammatory effects of doxazosin in rodent models of inflammation

Pharmacology. 2013;91(1-2):29-34. doi: 10.1159/000343762. Epub 2012 Nov 9.


Background: Doxazosin is an α(1)-adrenergic receptor antagonist for the treatment of high blood pressure and benign prostatic hyperplasia. Peripheral α-adrenergic receptors have been implicated in inflammation.

Aim: To examine the anti-inflammatory effects of doxazosin in rodent models of inflammation.

Method: The anti-inflammatory properties of doxazosin were investigated in 4 models. In all studies, drug treatment was administered 15 min prior to challenge. In the lipopolysaccharide (LPS)-induced systemic inflammation model, LPS was injected systemically at 0.25 mg/kg. At 90 min after challenge, blood samples were collected for analysis. In the LPS-induced pulmonary inflammation model, LPS was instilled intranasally. Four hours after challenge, the lungs were harvested for monocyte chemoattractant protein-1 (MCP-1) analysis. In a delayed-type hypersensitivity model, the mice were injected intravenously with sheep red blood cells, and rechallenged in the left footpad 7 days later. Drug treatment was given on day 6 and 7 just prior to the rechallenge. The thickness of hind footpads was measured at 15 min after rechallenge. In the thioglycollate-induced peritoneal monocyte infiltration model, mice were challenged with 3% thioglycollate, and 2 h later peritoneal lavage fluid was collected for MCP-1 analysis.

Results: In animals challenged systemically and intranasally with LPS, doxazosin inhibited TNF-α and MCP-1 production, respectively. In the delayed-type hypersensitivity model, footpad swelling was inhibited by doxazosin. Doxazosin decreased the level of MCP-1 release in the peritoneal cavity of thioglycollate-stimulated animals, though this effect was not statistically significant.

Conclusion: This is the first set of studies that reports the novel anti-inflammatory effects of doxazosin.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Chemokine CCL2 / immunology
  • Disease Models, Animal
  • Doxazosin / pharmacology
  • Doxazosin / therapeutic use*
  • Erythrocytes / immunology
  • Hypersensitivity, Delayed / drug therapy*
  • Hypersensitivity, Delayed / pathology
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred ICR
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy*
  • Peritonitis / immunology
  • Sheep
  • Thioglycolates
  • Tumor Necrosis Factor-alpha / immunology


  • Adrenergic alpha-1 Receptor Antagonists
  • Anti-Inflammatory Agents
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Lipopolysaccharides
  • Thioglycolates
  • Tumor Necrosis Factor-alpha
  • Doxazosin