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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels

Author(s): Lu Huang, Guangyin Xu*, Ruotian Jiang*, Yuncheng Luo , Yunxia Zuo and Jin Liu

Volume 20, Issue 1, 2022

Page: [16 - 26] Pages: 11

DOI: 10.2174/1570159X19666210407152528

Price: $65

Abstract

Two-pore domain potassium (K2P) channels are a diverse family of potassium channels. K2P channels generate background leak potassium currents to regulate cellular excitability and are thereby involved in a wide range of neurological disorders. K2P channels are modulated by a variety of physicochemical factors, such as mechanical stretch, temperature, and pH. In the peripheral nervous system, K2P channels are widely expressed in nociceptive neurons and play a critical role in pain perception. In this review, we summarize the recent advances in the pharmacological properties of K2P channels, with a focus on the exogenous small-molecule activators targeting K2P channels. We emphasize the subtype-selectivity, cellular and in vivo pharmacological properties of all the reported small-molecule activators. The key underlying analgesic mechanisms mediated by K2P are also summarized based on the data in the literature from studies using small-molecule activators and genetic knock-out animals. We discuss the advantages and limitations of the translational perspectives of K2P in pain medicine and provide outstanding questions for future studies in the end.

Keywords: Pain, analgesics, ion channels, potassium channels, peripheral nervous system, central nervous system.

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