Neuroscience & General Medicine PCU, EISAI Ltd, Hatfield, UK.
Future Med Chem. 2013 Sep;5(13):1525-46. doi: 10.4155/fmc.13.122.
The neuropeptide NK3 receptor is expressed almost exclusively within the mammalian nervous system and its localization is commensurate with a role in modulating central monoaminergic neurotransmission. Following on from our previous work we review the rationale for NK3 receptor antagonists as wide spectrum antipsychotics and the recent scientific and patent literature that has highlighted new chemical strategies to identify selective NK3 and dual activity NK1/3 receptor ligands for the putative treatment of schizophrenia. We discuss the emerging structural biology and its use in the design of molecules with increased structural diversity and predictable receptor pharmacology. Particular attention is paid to the progress in improving ligand drug-like properties. The status of imaging and the development of translational technologies in the neurokinin field are also discussed. Finally, we summarize the available clinical information on the compounds that have progressed into psychiatric patient populations and evaluate the potential therapeutic utility of NK3 receptor targeted ligands.
神经肽 NK3 受体几乎仅在哺乳动物神经系统中表达，其定位与调节中枢单胺能神经递质传递的作用相一致。继我们之前的工作之后，我们回顾了 NK3 受体拮抗剂作为广谱抗精神病药的基本原理，以及最近的科学和专利文献强调了新的化学策略，以确定用于潜在治疗精神分裂症的选择性 NK3 和双重活性 NK1/3 受体配体。我们讨论了新兴的结构生物学及其在设计具有增加的结构多样性和可预测的受体药理学的分子中的应用。特别关注改善配体药物样性质的进展。还讨论了神经激肽领域的成像和转化技术发展的现状。最后，我们总结了已进入精神科患者人群的化合物的可用临床信息，并评估了 NK3 受体靶向配体的潜在治疗效用。
