title: Ketotifen reduces sneezing but not histamine release following nasal challenge with antigen.
abstract: We evaluated the effect of pre-treatment with 1 and 2 mg b.i.d. of ketotifen on the early response to nasal challenge in a double-blind cross-over trial. Weekly nasal challenges were performed in 10 allergic subjects after 1 hr and 1, 2, 3 and 4 weeks of ketotifen administration. The response to nasal challenge was monitored by counting the number of sneezes, the assessment of subjective symptoms, and by measuring the levels of histamine and TAME-esterase activity in recovered nasal lavages. The number of sneezes diminished significantly after a single dose of drug with both the 1 and 2 mg doses. Prolonged pre-treatment did not improve the results. The levels of histamine and TAME-esterase activity in recovered nasal lavages were not changed significantly by either pre-treatment at either dose. Although the number of subjects was small, our data suggest that ketotifen diminishes allergic symptomatology by its antihistaminic properties rather than by inhibiting histamine release from mast cells. As we did not look into the effects of ketotifen on other products generated by mast cells (prostanoids, leukotrienes and tryptase), we cannot fully rule out an effect on mast cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
authors.forename: A M
authors.initials: AM
authors.lastname: Majchel
authors.forename: D
authors.initials: D
authors.lastname: Proud
authors.forename: A
authors.initials: A
authors.lastname: Kagey-Sobotka
authors.forename: L M
authors.initials: LM
authors.lastname: Lichtenstein
authors.forename: R M
authors.initials: RM
authors.lastname: Naclerio
mesh_terms: D000328:Adult; D000941:Antigens / Q000008:administration & dosage; D004311:Double-Blind Method; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007665:Ketotifen / Q000627:therapeutic use*; D009299:Nasal Provocation Tests; D010447:Peptide Hydrolases / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D012912:Sneezing / Q000187:drug effects
chemical_list: D000941:Antigens; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D007665:Ketotifen