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Cerebral Histamine H₁ Receptor Binding Potential Measured with PET Under a Test Dose of Olopatadine, an Antihistamine, Is Reduced After Repeated Administration of Olopatadine

¹ Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan; ² Department of Otorhinolaryngology, Kansai Medical University, Osaka, Japan; ³ Department of Mechanical Engineering, Kobe University, Kobe, Japan; and ⁴ Micron, Inc., Kobe, Japan

Correspondence: For correspondence or reprints contact: Michio Senda, Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. E-mail: senda{at}fbri.org

Some antihistamine drugs that are used for rhinitis and pollinosis have a sedative effect as they enter the brain and block the H₁ receptor, potentially causing serious accidents. Receptor occupancy has been measured with PET under single-dose administration in humans to classify antihistamines as more sedating or as less sedating (or nonsedating). In this study, the effect of repeated administration of olopatadine, an antihistamine, on the cerebral H₁ receptor was measured with PET. Methods: A total of 17 young men with rhinitis underwent dynamic brain PET with ¹¹C-doxepin at baseline, under an initial single dose of 5 mg of olopatadine (acute scan), and under another 5-mg dose after repeated administration of olopatadine at 10 mg/d for 4 wk (chronic scan). The H₁ receptor binding potential was estimated using Logan graphical analysis with cerebellum as reference region input. Results: The acute scan showed a slight decrease in H₁ receptor binding potential across the cerebral cortex (by 15% in the frontal cortex), but the chronic scan showed a marked decrease (by 45% from the acute scan in the frontal cortex). Behavioral data before and after the PET scans did not reveal any sedative effect. Conclusion: The results may be interpreted as either intracerebral accumulation of olopatadine or H₁ receptor downregulation due to repeated administration. The study shows feasibility and potential value for PET in evaluating the pharmacologic effect of a drug not only after a single dose but also after repeated administration.

Key Words: ¹¹C-doxepin • histamine H₁ receptor • olopatadine • PET • receptor occupancy

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JNM 2009 50: 11A-12A. [Full Text]