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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 ¦ÌM) to identify
possible activity of the compound. Results showing significant activity
in the initial screen were selected for ¦Êi 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.

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sltmac(½ð±Ò+1): ллӦÖú£¬»¶Ó­³£À´~~ 2011-07-22 16:11:22
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Binding Studies of the Initial Library Against a Panel of CNS Targets. ³õ²½ÎÄ¿â¶ÔÒ»×éÖÐÊàÉñ¾­ÏµÍ³°Ð±êµÄÇ׺ÍÐÔÑо¿
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.ÓÉÓÚÆäËüÌìÈ»´æÔÚµÄÕò¿È¼ÁÔÚÒ»¸ö»ò¶à¸öÖÐÊàÉñ¾­ÏµÍ³ÊÜÌå¾ßÓÐÇ¿µÄ¹¦ÄÜ£¬ÎÒÃÇÊÔͼȷ¶¨ÐÂË¹ÌæÄþÊÇ·ñÓëÕâЩÊÜÌå¾ßÓÐÇ׺ÍÐÔ¡£ Thus, synthetic ( )-neostenine and ( )-13-epineostenine were screened against 40 individual GPCR and other molecular targets (Fig. 2). Òò´Ë¶ÔºÏ³ÉµÄ( )-neostenineºÍ( )-13-epineostenine½øÐÐÁËÕë¶Ô40¸öGPCRºÍÆäËü·Ö×ӰбêµÄɸѡ¡£ The compounds were initially screened at a constant concentration (10 ¦ÌM) to identify possible activity of the compound. ³õ²½É¸Ñ¡²ÉÓù̶¨µÄŨ¶ÈÒÔÈ·¶¨»¯ºÏÎï¿ÉÄܵĻîÐÔ¡£Results showing significant activity in the initial screen were selected for ¦Êi determinations using radioligand binding assays.ÔÚ³õ²½É¸Ñ¡ÖÐÏÔʾÏÔÖø»îÐԵı»Ñ¡³öÀ´ÒÔ·ÅÉäÐÔÅäÌå½áºÏ²â¶¨È·¶¨Ki¡£ It was determined that ( )- neostenine and ( )-13-epineostenine only showed binding at the muscarinic M5 receptor and Sig-Rs, respectively, as shown. ½á¹ûÏÔʾ( )-neostenineºÍ( )-13-epineostenineÖ»·Ö±ð¶Ô¶¾Þ¦¼îM5ÊÜÌåºÍSig-RÏÔʾÇ׺ÍÐÔ¡£ The somewhat surprising binding differences observed between the epimers suggest a key role for the C-13 substituent.²îÏòÒì¹¹ÌåÖ®¼äÕâÖÖ¶àÉÙÁîÈ˾ªÒìµÄÇ׺ÍÐÔ²î±ðÌáʾC-13È¡´ú»ùµÄ¹Ø¼ü×÷Óá£
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