title: Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, a non-sedating antihistamine.
abstract: OBJECTIVE
  Histamine H1 receptor (H1R) antagonists often have sedative side effects, which are caused by the blockade of the neural transmission of the histaminergic neurons. We examined the brain H1R occupancy (H1RO) and the subjective sleepiness of levocetirizine, a new second-generation antihistamine, comparing fexofenadine, another non-sedating antihistamine, as a negative active control.
  
  
  METHODS
  Eight healthy volunteers underwent positron emission tomography (PET) imaging with [(11)C]doxepin, a PET tracer that specifically binds to H1Rs, after a single oral administration of levocetirizine (5 mg), fexofenadine (60 mg) or placebo in a double-blind crossover study. Binding potential ratios and H1ROs in the cerebral cortices regions were calculated using placebo. Subjective sleepiness was assessed with the Line Analogue Rating Scale and the Stanford Sleepiness Scale.
  
  
  RESULTS
  There was no significant difference between the mean brain H1RO after levocetirizine administration (8.1%; 95% CI: -9.8 to 26.0%) and fexofenadine administration (-8.0%; 95% CI: -26.7 to 10.6%). Similarly, subjective sleepiness was not significantly different between the two antihistamines and placebo. Neither subjective sleepiness nor plasma concentrations was significantly correlated with the brain H1RO of the two antihistamines.
  
  
  CONCLUSIONS
  At therapeutic dose, levocetirizine does not bind significantly to the brain H1Rs and does not induce significant sedation.
authors.affiliation: Tohoku University, Cyclotron and Radioisotope Center, Division of Cyclotron Nuclear Medicine , 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578 , Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hiraoka
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Thomas
authors.initials: T
authors.lastname: Grobosch
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Keiichi
authors.initials: K
authors.lastname: Oda
authors.forename: Jun
authors.initials: J
authors.lastname: Toyohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000284:Administration, Oral; D001921:Brain / Q000187:drug effects*; D002250:Carbon Radioisotopes; D017332:Cetirizine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004316:Doxepin; D039563:Histamine H1 Antagonists, Non-Sedating / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D016593:Terfenadine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D004316:Doxepin; C472067:levocetirizine; D016593:Terfenadine; C093230:fexofenadine; D017332:Cetirizine
keywords: antihistamine; histamine H1 receptor occupancy; levocetirizine; positron emission tomography; sedating side effect