title: The effects of an H3 receptor antagonist (PF-03654746) with fexofenadine on reducing allergic rhinitis symptoms.
abstract: BACKGROUND
  Nasal H(3) receptors might have a role in mediating the effects of histamine in patients with allergic rhinitis.
  
  
  OBJECTIVE
  This study explored the effect of the potent oral H(3) receptor antagonist PF-03654746 in combination with an oral H(1) receptor antagonist on the objective (acoustic rhinometry) and subjective (symptoms) responses to nasal allergen challenge.
  
  
  METHODS
  Twenty patients with out-of-season allergic rhinitis displaying a 30% or greater decrease in minimum nasal cross-sectional area (A(min)) after bolus (ragweed) complete nasal allergen challenge at screening were studied by using a randomized, double-blind, single-dose, 4-way crossover design. Treatments included 10 mg of PF-03654746 plus 60 mg of fexofenadine (group 1), 1 mg of PF-03654746 plus 60 mg of fexofenadine (group 2), 60 mg of fexofenadine/120 mg of pseudoephedrine (group 3), and placebo (group 4). After dosing, subjects underwent complete nasal allergen challenge. Nasal symptom scores (no. of sneezes and 0- to 5-point scores for severity of congestion, itching, and rhinorrhea), A(min) (in square centimeters), and nasal volume (in cubic centimeters) were recorded 15, 30, 45, and 60 minutes after allergen. There was a minimum 10-day washout between periods.
  
  
  RESULTS
  The following symptom scores were significantly (P ≤ .05) reduced by active treatments versus placebo: group 1, congestion of -0.7 (SE, 0.3), itching of -1.0 (SE, 0.3), rhinorrhea of -1.3 (SE, 0.3), and sneeze of -8.8 (SE, 1.5); group 2, itching of -0.6 (SE, 0.3), rhinorrhea of -0.8 (SE, 0.3), and sneeze of -9.1 (SE, 1.5); and group 3, rhinorrhea of -0.7 (SE, 0.3) and sneeze of -7.0 (SE, 1.5). There was no significant effect of any treatment on mean A(min) proportion or nasal volume proportion after nasal allergen challenge.
  
  
  CONCLUSIONS
  In combination with fexofenadine, single doses of PF-03654746 caused a reduction in allergen-induced nasal symptoms. H(3) receptor antagonism might be a novel therapeutic strategy to further explore in patients with allergic rhinitis.
authors.affiliation: Department of Medicine, Division of Allergy/Immunology, Creighton University School Medicine, Omaha, Neb 68131, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Stokes
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Romero
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Allan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Phillips
authors.forename: Frances
authors.initials: F
authors.lastname: Hackman
authors.forename: Janie
authors.initials: J
authors.lastname: Misfeldt
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Casale
mesh_terms: D000328:Adult; D031164:Ambrosia / Q000276:immunology; D018926:Anti-Allergic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003503:Cyclobutanes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects / Q000627:therapeutic use*; D054828:Histamine H3 Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D012882:Skin Tests; D016593:Terfenadine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018926:Anti-Allergic Agents; D003503:Cyclobutanes; D004338:Drug Combinations; D039563:Histamine H1 Antagonists, Non-Sedating; D054828:Histamine H3 Antagonists; C569672:N-ethyl-3-fluoro-3-(3-fluoro-4-(pyrrolidinylmethyl)phenyl)cyclobutanecarboxamide; D011759:Pyrrolidines; D016593:Terfenadine; C093230:fexofenadine