4.7 Article

Small molecule ligands for α9*and α7 nicotinic receptors: A survey and an update, respectively

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PHARMACOLOGICAL RESEARCH
卷 193, 期 -, 页码 -

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ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2023.106801

关键词

alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR); alpha 9 nicotinic acetylcholine receptor (alpha 9-nAChR); alpha 9 alpha 10 nicotinic acetylcholine receptor (v9 alpha 10-nAChR); Orthosteric ligands; Allosteric ligands; Radiochemicals

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The alpha 9- and alpha 7-containing nicotinic acetylcholine receptors play key roles in physiological and pathological processes. Selective ligands for these receptors are important research tools and potential therapeutic agents. While there is a wealth of information on alpha 7-nAChR ligands, the understanding of selective alpha 9-nAChR ligands is limited. This review provides a comprehensive overview of the latter, along with recent updates on alpha 7-nAChR ligands.
The alpha 9- and alpha 7-containing nicotinic acetylcholine receptors (nAChRs) mediate numerous physiological and pathological processes by complex mechanisms that are currently the subject of intensive study and debate. In this regard, selective ligands serve as invaluable investigative tools and, in many cases, potential therapeutics for the treatment of various CNS disfunctions and diseases, neuropathic pain, inflammation, and cancer. However, the present scenario differs significantly between the two aforementioned nicotinic subtypes. Over the past few decades, a large number of selective alpha 7-nAChR ligands, including full, partial and silent agonists, antagonists, and allosteric modulators, have been described and reviewed. Conversely, reports on selective alpha 9-containing nAChR ligands are relatively scarce, also due to a more recent characterization of this receptor subtype, and hardly any focusing on small molecules. In this review, we focus on the latter, providing a comprehensive overview, while providing only an update over the last five years for alpha 7-nAChR ligands.

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