人类药理学方法在基于 TRP 离子通道的镇痛药物开发中的应用。

Human pharmacological approaches to TRP-ion-channel-based analgesic drug development.

机构信息

Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.

出版信息

Drug Discov Today. 2018 Dec;23(12):2003-2012. doi: 10.1016/j.drudis.2018.06.020. Epub 2018 Jun 30.

DOI:10.1016/j.drudis.2018.06.020

PMID:29969684

Abstract

The discovery of novel analgesic drug targets is an active research topic owing to insufficient treatment options for persisting pain. Modulators of temperature-sensing transient receptor potential ion channels (thermoTRPs), in particular TRPV1, TRPV2, TRPM8 and TRPA1, have reached clinical development. This requires access for TRP channels and the effects of specific modulators in humans. This is currently possible via (i) the study of TRP channel function in human-derived cell lines, (ii) immunohistochemical visualization of TRP channel expression in human tissues, (iii) human experimental pain models employing sensitization by means of topical application of TRP channel activators including capsaicin (TRPV1), menthol (TRPM8), mustard oil and cinnamaldehyde (TRPA1), and (iv) the study of phenotypic consequences of human TRP gene variants.

摘要

新型镇痛药物靶点的发现是一个活跃的研究课题，因为持续疼痛的治疗选择有限。温度感应瞬时受体电位离子通道（thermoTRPs）调节剂，特别是 TRPV1、TRPV2、TRPM8 和 TRPA1，已进入临床开发。这需要 TRP 通道的通路和特定调节剂在人体中的作用。目前这可以通过以下方式实现：（i）在人源细胞系中研究 TRP 通道功能，（ii）在人组织中免疫组织化学可视化 TRP 通道表达，（iii）使用 TRPV1 激动剂（辣椒素）、TRPM8 激动剂（薄荷醇）、芥末油和肉桂醛（TRPA1）进行局部应用以敏化的人类实验性疼痛模型，以及（iv）研究人类 TRP 基因变异的表型后果。