组胺H1-receptor入住率在人类大脑的神经成像正电子发射断层扫描(PET): ebastine的比较研究,第二代抗组胺剂,和(+)扑尔敏,经典的抗组胺剂。
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Tagawa M,卡诺M,冈N, Higuchi M,松田M, Y,水木Arai H,岩田聪R,藤井裕久T, Komemushi年代,被罩T,伊藤M,佐佐木H,渡边T,柳井正K
组胺H1-receptor入住率在人类大脑的神经成像正电子发射断层扫描(PET): ebastine的比较研究,第二代抗组胺剂,和(+)扑尔敏,经典的抗组胺剂。
Br中国新药杂志。2001年11月,52 (5):501 - 9。
- PubMed ID
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11736858 (在PubMed]
- 文摘
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目的:引起的镇静抗组胺药被广泛公认的引起的渗透穿过血脑屏障的大脑组织胺H1-receptors占领。我们以前学习的机制引起的镇静抗组胺药使用正电子发射断层扫描(PET)。最近,我们揭示了nonsedative ebastine特点,第二代抗组胺剂,与认知性能测试。在目前的研究中,由ebastine H1-receptor占领了人类的大脑使用宠物。方法:Ebastine 10毫克和(+)氯苯那敏2或6毫克口服给健康男性志愿者。PET扫描与c[11]多虑平,一个强有力的H1-receptor拮抗剂,最高温度附近进行各自的药物。其他志愿者在对照组还收到了PET扫描。绑定的潜力多虑平(BP = Bmax / Kd)可用大脑H1-receptors成像voxel-by-voxel基础上通过图形分析。通过设置感兴趣的区域,计算药物的H1-receptor入住率在几个H1-receptor富裕地区。结果:大脑放射性分布ebastine治疗后相似,没有任何药物。 However, after the oral administration of 2 mg (+)-chlorpheniramine, the level was lower than after ebastine and nondrug treatments. Graphical analysis followed by statistical parametric mapping (SPM96) revealed that H1-receptor rich regions such as cortices, cingulate gyrus and thalamus were regions where the BPs after ebastine were significantly higher than after (+)-chlorpheniramine (2 mg). H1-receptor occupancies in cortex were approximately 10% by ebastine and > or = 50% by either dose of (+)-chlorpheniramine (95% confidence interval for difference in the mean receptor occupancies: 27%, 54% for 2 mg and 35%, 62% for 6 mg vs ebastine, respectively). Receptor occupancies increased with increasing plasma concentration of (+)-chlorpheniramine, but not with concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine (10 mg orally) causes brain histamine H1-receptor occupation of approximately 10%, consistent with its lower incidence of sedative effect, whereas (+)-chlorpheniramine occupied about 50% of brain H1-receptors even at a low but sedative dose of 2 mg; occupancy of (+)-chlorpheniramine was correlated with plasma (+)-chlorpheniramine concentration.