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.
- histamine H1 receptor occupancy
- positron emission tomography (PET)
- proportional impairment ratio