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Bioorg Med Chem Lett
2005 Sep 01;1517:3874-80. doi: 10.1016/j.bmcl.2005.05.118.
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The characterization of a novel rigid nicotine analog with alpha7-selective nAChR agonist activity and modulation of agonist properties by boron inclusion.
Papke RL
,
Zheng G
,
Horenstein NA
,
Dwoskin LP
,
Crooks PA
.
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The alpha7 nAChR subtype is of particular interest as a potential therapeutic target since it has been implicated as a mediator of both cognitive and neuroprotective activity. The rigid nicotine analog ACME and the N-cyanoborane conjugate ACME-B are selective partial agonists of rat alpha7 receptors expressed in Xenopus oocytes, with no significant activation of either alpha3beta4 or alpha4beta2 receptors. ACME-B is both more potent and efficacious than ACME. The efficacies of ACME-B and ACME are approximately 26% and 10% of the efficacy of ACh, respectively. Similar N-conjugation of S(-)nicotine with cyanoborane decreased efficacy for alpha3beta4 and alpha4beta2 receptors, as well as for alpha7 nAChR. Structural comparison of ACME with the benzylidene anabaseines, another class of previously identified alpha7-selective agonists, suggests that they share a similar structural motif that may be applicable to other alpha7-selective agonists.
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