Senda Michio, Kubo Nobuo, Adachi Kazuhiko, Ikari Yasuhiko, Matsumoto Keiichi, Shimizu Keiji, Tominaga Hideyuki
Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan.
J Nucl Med. 2009 Jun;50(6):887-92. doi: 10.2967/jnumed.108.058537. Epub 2009 May 14.
Some antihistamine drugs that are used for rhinitis and pollinosis have a sedative effect as they enter the brain and block the H(1) 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 H(1) receptor was measured with PET.
A total of 17 young men with rhinitis underwent dynamic brain PET with (11)C-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 H(1) receptor binding potential was estimated using Logan graphical analysis with cerebellum as reference region input.
The acute scan showed a slight decrease in H(1) 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.
The results may be interpreted as either intracerebral accumulation of olopatadine or H(1) 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.
一些用于治疗鼻炎和花粉症的抗组胺药物进入大脑并阻断H(1)受体时会产生镇静作用，可能导致严重事故。在人体单剂量给药情况下，已通过正电子发射断层扫描（PET）测量受体占有率，以将抗组胺药物分类为更具镇静作用或镇静作用较小（或无镇静作用）。在本研究中，使用PET测量抗组胺药物奥洛他定重复给药对大脑H(1)受体的影响。
共有17名患有鼻炎的年轻男性在基线时、初始单剂量5毫克奥洛他定给药后（急性扫描）以及在10毫克/天的奥洛他定重复给药4周后给予另一5毫克剂量后（慢性扫描），接受了用(11)C-多塞平进行的动态脑PET检查。使用以小脑作为参考区域输入的洛根图形分析法估计H(1)受体结合潜力。
急性扫描显示大脑皮层H(1)受体结合潜力略有下降（额叶皮层下降15%），但慢性扫描显示显著下降（额叶皮层较急性扫描下降45%）。PET扫描前后的行为数据未显示任何镇静作用。
结果可解释为奥洛他定在脑内蓄积或由于重复给药导致H(1)受体下调。该研究表明PET在评估药物不仅在单剂量后而且在重复给药后的药理作用方面具有可行性和潜在价值。
