Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine-Δ2 -Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation
نویسندگان
چکیده
منابع مشابه
Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor.
We introduce the term 'silent agonists' to describe ligands that can place the α7 nicotinic acetylcholine receptor (nAChR) into a desensitized state with little or no apparent activation of the ion channel, forming a complex that can subsequently generate currents when treated with an allosteric modulator. KC-1 (5'-phenylanabaseine) was synthesized and identified as a new silent agonist for the...
متن کاملSynthesis of selective agonists for the α7 nicotinic acetylcholine receptor with in situ click-chemistry on acetylcholine-binding protein templates.
The acetylcholine-binding proteins (AChBPs), which serve as structural surrogates for the extracellular domain of nicotinic acetylcholine receptors (nAChRs), were used as reaction templates for in situ click-chemistry reactions to generate a congeneric series of triazoles from azide and alkyne building blocks. The catalysis of in situ azide-alkyne cycloaddition reactions at a dynamic subunit in...
متن کاملThe minimal pharmacophore for silent agonism of the α7 nicotinic acetylcholine receptor.
The minimum pharmacophore for activation of the human α7 nicotinic acetylcholine receptor (nAChR) is the tetramethylammonium cation. Previous work demonstrated that larger quaternary ammonium compounds, such as diethyldimethylammonium or 1-methyl quinuclidine, were α7-selective partial agonists, but additional increase in the size of the ammonium cation or the quinuclidine N-alkyl group by a si...
متن کاملSynthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor
Article history: Received 14 February 2013 Revised 8 May 2013 Accepted 13 May 2013 Available online 23 May 2013
متن کاملElectrophysiological perspectives on the therapeutic use of nicotinic acetylcholine receptor partial agonists.
Partial agonist therapies rely variously on two hypotheses: the partial agonists have their effects through chronic low-level receptor activation or the partial agonists work by decreasing the effects of endogenous or exogenous full agonists. The relative significance of these activities probably depends on whether acute or chronic effects are considered. We studied nicotinic acetylcholine rece...
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ژورنال
عنوان ژورنال: ChemMedChem
سال: 2017
ISSN: 1860-7179
DOI: 10.1002/cmdc.201700162