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烟云听雨铁杆木虫 (正式写手)
金虫
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[求助]
求翻译一段英文文献（药化）
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Binding Studies of the Initial Library Against a Panel of CNS Targets. Because other naturally occurring antitussive agents have potent function at one or more CNS receptors (i.e., codeine, along with numerous related agents) (40), we sought to determine if neostenine bound to such targets. Thus, synthetic ()-neostenine and ()-13-epineostenine were screened against 40 individual GPCR and other molecular targets (Fig. 2). The compounds were initially screened at a constant concentration (10 μM) to identify possible activity of the compound. Results showing significant activity in the initial screen were selected for κi determinations using radioligand binding assays. It was determined that ()- neostenine and ()-13-epineostenine only showed binding at the muscarinic M5 receptor and Sig-Rs, respectively, as shown. The somewhat surprising binding differences observed between the epimers suggest a key role for the C-13 substituent. Notably, neither of the naturally occurring alkaloids tested had activity at any of the opioid receptors. Although Sig-R binding mediates the activity of some nonnarcotic antitussive agents, such as dextrophan (41), the lack of Sig-R binding in neostenine indicates that the source of this antitussive activity of this compound is still unknown. Target identification studies, along with the independent validation of the in vivo literature results, are called for but beyond the scope of the present paper. |
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