Brain histamine H1 receptor occupancy of loratadine measured by positron emission topography: Comparison of H1 receptor occupancy and proportional impairment ratio

Nobuo Kubo, Michio Senda, Yasunori Ohsumi, Setsu Sakamoto, Keiichi Matsumoto, Manabu Tashiro, Nobuyuki Okamura, Kazuhiko Yanai

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aims 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 10mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2mg, 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 10mg and d-chlorpheniramine 2mg 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 10mg and d-chlorpheniramine 2mg. Results Loratadine 10mg occupied 11.7±19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2mg occupied 53.0±33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10mg. 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). Conclusion Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalHuman Psychopharmacology
Volume26
Issue number2
DOIs
Publication statusPublished - 2011 Mar

Keywords

  • H1-antihistamine
  • histamine H1 receptor occupancy
  • loratadine
  • non-sedating
  • positron emission tomography (PET)
  • proportional impairment ratio

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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