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ChemicalBook >> journal list >> Proceedings for Annual Meeting of The Japanese Pharmacological Society >>article

Brain histamine H1 receptor occupancy measured by PET after oral administration of desloratadine and loratadine

Published:1 January 2019 DOI: 10.1254/JPSSUPPL.92.0_3-O-25
Tadaho Nakamura,?K. Hiraoka,?R. Harada,?T. Matsuzawa,?T. Yoshikawa,?M. Tashiro,?K. Yanai,?N. Okamura

Abstract

Objective: Some histamine H1 receptor (H1R) antagonists have sedative effects, caused by the blockade of histamine neural transmission. Desloratadine is a newly-marked antihistamine, but its sedative properties have not been examined by positron emission tomography (PET). We examined the brain H1R binding potential ratio (BPR), H1R occupancy (H1RO) and the subjective sleepiness after oral administration of desloratadine and loratadine, the prodrug of desloratadine. Methods: Eight healthy male volunteers underwent PET imaging with [C]doxepin after single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPRs and H1ROs in the cerebral cortices were calculated. Subjective sleepiness was quantified by the LARS and the SSS. Results: BPR after loratadine administration was significantly lower than placebo (p<0.05), but BPR after desloratadine was not significant. There was no significant difference, however, between H1RO after desloratadine and loratadine administration. The subjective sleepiness was not significantly different among the two antihistamines and placebo. Conclusion: At therapeutic dose, desloratadine did not bind significantly to brain H1Rs and did not cause significant sedation. Oral Sessions

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