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Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels
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 physicochemic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199554/ https://www.ncbi.nlm.nih.gov/pubmed/33827408 http://dx.doi.org/10.2174/1570159X19666210407152528 |
Sumario: | 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. |
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