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

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.