Truxillic Acid Derivatives, Neuromuscular Blocking Agents with Very High Affinity for the Allosteric Binding Site of Muscarinic Acetylcholine Receptors

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Title:Truxillic Acid Derivatives, Neuromuscular Blocking Agents with Very High Affinity for the Allosteric Binding Site of Muscarinic Acetylcholine Receptors
Creators:
Urbanský, Marek
Proška, Jan
Říčný, Jan
Drašar, Pavel
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 64, 12, pp. 1980-1992
Uncontrolled Keywords:Cooperativity, Muscarinic receptors, Quaternary ammonium salts, Truxillic acid, Cyclobutanes, Nicotinic receptors, Allosteric binding

Abstract

Bis-quaternary salts of 3-piperidinopropyl esters of α-truxillic acid were synthesized in order to study their allosteric action on muscarinic acetylcholine receptor. Using radioligand binding studies, it has been demonstrated that most of prepared compounds bind with high affinity to the allosteric binding site of M<sub>2</sub> muscarinic receptor subtype (<i>K</i><sub>d</sub> values in the range 1-10 nM). Bulky substitution of the quaternary ammonium center led to effective positive modulators of [<sup>3</sup>H]<i>N</i>-methylscopolamine binding to M<sub>2</sub> receptors. Due to its high allosteric potency, the structure of phenacyl derivative seems to be the most promising candidate for future design of photoaffinity probes or radiolabelled ligands for mapping the allosteric binding site. <p>

Title:Truxillic Acid Derivatives, Neuromuscular Blocking Agents with Very High Affinity for the Allosteric Binding Site of Muscarinic Acetylcholine Receptors
Creators:
Urbanský, Marek
Proška, Jan
Říčný, Jan
Drašar, Pavel
Uncontrolled Keywords:Cooperativity, Muscarinic receptors, Quaternary ammonium salts, Truxillic acid, Cyclobutanes, Nicotinic receptors, Allosteric binding
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:64
Number:12
Page Range:pp. 1980-1992
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19991980UNSPECIFIED
ID Code:1610
Item Type:Article
Deposited On:06 Feb 2009 17:11
Last Modified:06 Feb 2009 16:11

Citation

Urbanský, Marek; Proška, Jan; Říčný, Jan; Drašar, Pavel (1999) Truxillic Acid Derivatives, Neuromuscular Blocking Agents with Very High Affinity for the Allosteric Binding Site of Muscarinic Acetylcholine Receptors. Collection of Czechoslovak Chemical Communications, 64 (12). pp. 1980-1992. ISSN 0010-0765

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