In vitro pharmacology of clinically used central nervous system-active drugs as inverse H1 receptor agonists
In vitro pharmacology of clinically used central nervous system-active drugs as inverse H1 receptor agonists
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DOI：
10.1124/jpet.106.118869
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发表时间：
2007-07-01
影响因子：
3.5
通讯作者：
Weiner, D. M.
中科院分区：
文献类型：
--
作者：
Bakker, R. A.;Nicholas, M. W.;Weiner, D. M.
人组胺H-1受体（H1R）是一种典型的G蛋白偶联受体，是开发治疗过敏性疾病的拮抗剂的重要靶点。许多神经精神药物也已知能有效拮抗这种受体，这是其副作用的潜在方面。我们使用基于细胞的受体选择和扩增技术测定，通过评估bbb130治疗药物和参考药物的功能受体活性，进一步确定人类H1R的临床药理学。基于这一筛选，我们已经报道了8R-lisuride作为一种有效的立体特异性部分H1R激动剂的鉴定（Mol Pharmacol 65: 538 - 549, 2004）。相比之下，本文报告了大量不同临床和化学类别的药物，这些药物在中枢神经系统中具有活性，显示出有效的H1R逆激动剂活性。这些临床相关的穿透脑药物的绝对功能效力和等级顺序可能用于预测其临床概况的各个方面，包括镇静倾向。
The human histamine H-1 receptor ( H1R) is a prototypical G protein- coupled receptor and an important, well characterized target for the development of antagonists to treat allergic conditions. Many neuropsychiatric drugs are also known to potently antagonize this receptor, underlying aspects of their side effect profiles. We have used the cell- based receptor selection and amplification technology assay to further define the clinical pharmacology of the human H1R by evaluating > 130 therapeutic and reference drugs for functional receptor activity. Based on this screen, we have reported on the identification of 8R-lisuride as a potent stereospecific partial H1R agonist ( Mol Pharmacol 65: 538 - 549, 2004). In contrast, herein we report on a large number of varied clinical and chemical classes of drugs that are active in the central nervous system that display potent H1R inverse agonist activity. Absolute and rank order of functional potency of these clinically relevant brain- penetrating drugs may possibly be used to predict aspects of their clinical profiles, including propensity for sedation.