Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine
Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine
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口服地氯雷他定和氯雷他定后脑组胺 H1 受体占用情况
DOI：
10.1002/prp2.499
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发表时间：
2019
影响因子：
2.6
通讯作者：
Okamura Nobuyuki
中科院分区：
文献类型：
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作者：
Nakamura Tadaho;Hiraoka Kotaro;Harada Ryuichi;Matsuzawa Takuro;Ishikawa Yoichi;Funaki Yoshihito;Yoshikawa Takeo;Tashiro Manabu;Yanai Kazuhiko;Okamura Nobuyuki
一些组胺H1受体(H1R)拮抗剂通过阻断组胺在大脑中的传递而引起不良镇静反应。地洛他定是第二代抗组胺药物，用于治疗过敏性疾病。它与脑H1Rs的结合是抗组胺药物镇静作用的基础，以前还没有在人脑中用正电子发射断层扫描(PET)检测过。我们检测了口服地洛他定和氯雷他定后的脑部H1R结合电势比(BPR)、H1R占有率(H1RO)和主观嗜睡情况。在一项双盲交叉研究中，8名健康男性志愿者在单次口服地洛他定(5 Mg)、氯雷他定(10 Mg)或安慰剂后，用[11C]-doxepin进行了PET成像，[11C]-doxepin是一种追踪H1Rs的PET示踪剂。计算大脑皮层BPR和H1RO，测定氯雷他定和地洛他定的血药浓度。主观嗜睡度采用线类比评定量表(LARS)和斯坦福嗜睡量表(SSS)进行量化。氯雷他定组BPR显著低于安慰剂组(0.504±0.074比0.584±0.059，P<0.05)，但地洛他定组与安慰剂组比较差异无统计学意义(0.546±0.084比0.584±0.059，P=0.250)。氯雷他定血药浓度与BPR呈负相关，地洛他定血药浓度与BPR无相关性。地洛他定和氯雷他定脑H1RO分别为6.47%±10.5%和13.8%±77.00%(P=0.103)。在接受这两种抗组胺药物和安慰剂的受试者中，主观嗜睡感没有显著差异。在治疗剂量下，地洛他定与脑H1Rs没有显著结合，也没有诱导任何显著的镇静作用。
Some histamine H1receptor (H1R) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second‐generation antihistamine for treatment of allergic disorders. Its binding to brain H1Rs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain H1R binding potential ratio (BPR), H1R occupancy (H1RO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [11C]‐doxepin, a PET tracer for H1Rs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double‐blind crossover study. BPR and H1RO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD],P<0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059,P= 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain H1ROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (P=0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain H1Rs and did not induce any significant sedation.