title: Effects of the inverse alpha-agonist doxazosin in allergic rhinitis.
abstract: We examined the paradoxical hypothesis that the alpha-receptor inverse agonist doxazosin might produce beneficial effects in allergic rhinitis.
  
  
  
  To evaluate single and chronic dosing effects of doxazosin on nasal airflow and symptoms in allergic rhinitis.
  
  
  
  Fifteen patients randomized to receive 3-5 weeks of oral doxazosin 4 mg daily or placebo in crossover fashion. Measurements were taken at baseline and after first and last doses.
  
  
  
  There was a fall in peak nasal inspiratory flow (PNIF) between baseline vs. first dose of doxazosin: mean difference -19 L/min (95% CI -35 to -2) P = 0.03, with recovery between first and last doses: 21 L/min (95% CI 7-34) P = 0.006. Nasal visual analogue scale (VAS) and blockage scores were worse between baseline vs. first dose of doxazosin: mean difference VAS -10 mm (95% CI -18 to -2) P = 0.02, blockage -0.7 (95% CI -1.3 to -0.1) P = 0.02, with recovery between first and last doses: VAS 15 mm (95% CI 4-25) P = 0.009, blockage 1.1 (95% CI 0.5-1.6) P = 0.001. The oxymetazoline dose-response for PNIF was blunted after single vs chronic dosing with doxazosin: mean difference -17 L/min (95% CI -30 to -4) P = 0.01. Heart rate and diastolic blood pressure showed the same pattern. There was a significant difference between doxazosin and placebo for nasal blockage score and heart rate after single but not chronic dosing.
  
  
  
  There was a disconnect between single and chronic dosing effects of doxazosin for nasal symptoms, oxymetazoline response and cardiovascular outcomes, in turn suggesting alpha-1 receptor up-regulation.
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: A
authors.initials: A
authors.lastname: Manoharan
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Morrison
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D017292:Doxazosin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009299:Nasal Provocation Tests; D065631:Rhinitis, Allergic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012882:Skin Tests; D016896:Treatment Outcome
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D015415:Biomarkers; D017292:Doxazosin
keywords: Allergic rhinitis; alpha-receptor antagonist; alpha-receptor inverse agonist; doxazosin; peak nasal inspiratory flow