Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin

Manabu Tashiro, Xudong Duan, Motohisa Kato, Masayasu Miyake, Shoichi Watanuki, Yoichi Ishikawa, Yoshihito Funaki, Ren Iwata, Masatoshi Itoh, Kazuhiko Yanai

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57 Citations (Scopus)


AIMS: Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H1 receptor occupancy (H1RO) in the brain using positron emission tomography (PET). The aim was to measure H 1RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine. METHODS: Eight healthy male volunteers (mean age ± SD 24.4 ± 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with 11C-doxepin in a crossover study design. Binding potential ratio and H1ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H1RO was examined. RESULTS: H1RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H1ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H1ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001). CONCLUSION: Oral bepotastine (10 mg), with its relatively low H1RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.

Original languageEnglish
Pages (from-to)811-821
Number of pages11
JournalBritish journal of clinical pharmacology
Issue number6
Publication statusPublished - 2008 Jun


  • First-generation antihistamine
  • Histamine H receptor occupancy
  • Placebo-controlled crossover study design
  • Positron emission tomography
  • Second-generation antihistamine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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