title: Brain histamine H1 receptor occupancy of loratadine measured by positron emission topography: comparison of H1 receptor occupancy and proportional impairment ratio.
abstract: OBJECTIVE
  We have evaluated the sedative properties of H1-antihistamines by using positron emission tomography (PET) and ¹¹C-doxepin. The purpose of the present study was to measure histamine H1 receptor occupancy (H1RO) of loratadine 10 mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2 mg, a first-generation antihistamine. We also compared our PET findings with the proportional impairment ratio reported by McDonald et al.
  
  
  METHODS
  The H1RO of loratadine 10 mg and d-chlorpheniramine 2 mg were evaluated in human brains in a double-blind and crossover design using ¹¹C-doxepin PET. Eleven young male patients with allergic rhinitis were examined by PET following oral single administration of loratadine 10 mg and d-chlorpheniramine 2 mg.
  
  
  RESULTS
  Loratadine 10 mg occupied 11.7 ± 19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2 mg occupied 53.0 ± 33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10 mg. The H1RO values of loratadine and d-chlorpheniramine as well as those of previous studies were found to be significantly proportional to the proportional impairment ratio (r = 0.899).
  
  
  CONCLUSIONS
  Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity.
authors: Department of Otolaryngology, Kansai Medical University, Osaka, Japan.
authors: Nobuo
authors: N
authors: Kubo
authors: Michio
authors: M
authors: Senda
authors: Yasunori
authors: Y
authors: Ohsumi
authors: Setsu
authors: S
authors: Sakamoto
authors: Keiichi
authors: K
authors: Matsumoto
authors: Manabu
authors: M
authors: Tashiro
authors: Nobuyuki
authors: N
authors: Okamura
authors: Kazuhiko
authors: K
authors: Yanai
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000378:metabolism; D006801:Humans; D017336:Loratadine / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D017336:Loratadine