Subtype‐selective inhibition of [methyl‐3H]‐N‐methylscopolamine binding to muscarinic receptors by α‐truxillic acid esters

@article{Lyskov1999SubtypeselectiveIO,
  title={Subtype‐selective inhibition of [methyl‐3H]‐N‐methylscopolamine binding to muscarinic receptors by $\alpha$‐truxillic acid esters},
  author={Michaela Lys{\'i}kov{\'a} and Květoslava Fuksov{\'a} and Tomas Elbert and Jan Jakub{\'i}k and Stanislav Tuc̆ek},
  journal={British Journal of Pharmacology},
  year={1999},
  volume={127}
}
Seven esters of α‐truxillic acid have been synthesized: bis‐3‐piperidylpropyl ester and its quaternary bis‐N‐ethyl derivative, bis‐N‐diethylaminopropyl ester and its quaternary bis‐N‐methyl derivative, and bis‐4‐piperidylbutyl ester and its quaternary bis‐N‐methyl and bis‐N‐ethyl derivatives. All esters inhibited the specific binding of muscarinic receptor antagonist [methyl‐3H]‐N‐methylscopolamine ([3H]‐NMS) to muscarinic receptors in membranes of CHO cell lines stably expressing the human… Expand
Muscarinic Allosteric Modulators: Atypical Structure‐Activity‐Relationships in Bispyridinium‐type Compounds
TLDR
It is concluded that DUO compounds bind in an “atypical” manner which is in agreement with recently reported side‐directed mutagenesis and molecular modeling studies. Expand
Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors.
TLDR
Data point to an important role of o3 loop in the mechanism of the positive and negative cooperativity between [(3)H]NMS and alcuronium and gallamine, respectively, and in the binding of both modulators to M(2) receptors, and reveal independence between mutation-induced changes in the affinity for a modulator and inThe magnitude and direction of the allosteric effect of the modulator. Expand
Bisquaternary caracurine V derivatives as allosteric modulators of ligand binding to M2 acetylcholine receptors.
TLDR
Molecular modeling studies indicated that the caracurine V ring system satisfies the pharmacophore model for the allosteric interaction and suggests a sterically restricted binding pocket. Expand
Interactions between Allosteric Modulators and 4-DAMP and Other Antagonists at Muscarinic Receptors: Potential Significance of the Distance between the N and Carboxyl C Atoms in the Molecules of Antagonists
TLDR
Positive effects of alcuronium, strychnine and brucine on the affinity of the M2 receptors for 4-DAMP have been confirmed by direct measurements of the binding of [3H]-4-diphenylacetoxy-N-dimethylpiperidinium. Expand
Asparagine, Valine, and Threonine in the Third Extracellular Loop of Muscarinic Receptor Have Essential Roles in the Positive Cooperativity of Strychnine-Like Allosteric Modulators
TLDR
This work reports the first evidence of constitution of positive cooperativity of WGA by switching sequences of two parental receptors, both exhibiting negative cooperativity, and suggests that these amino acids are essential for propagation of a conformation change resulting inpositive cooperativity induced by these modulators. Expand
Stereoselective Synthesis of 1,3-Diaminotruxillic Acid Derivatives: An Advantageous Combination of C-H-ortho-Palladation and On-Flow [2+2]-Photocycloaddition in Microreactors.
TLDR
The stereoselective synthesis of ε-isomers of dimethyl esters of 1,3-diaminotruxillic acid derivatives as single isomers using LED light sources with different wavelengths in flow microreactors is reported. Expand
Allosteric Modulation of Muscarinic Acetylcholine Receptors
TLDR
This review summarizes over 30 years of research on the molecular mechanisms of allosteric interactions of drugs with the receptor and for newAllosteric modulators of muscarinic receptors with potential therapeutic use. Expand
Metal-Free [2 + 2]-Photocycloaddition of (Z)-4-Aryliden-5(4H)-Oxazolones as Straightforward Synthesis of 1,3-Diaminotruxillic Acid Precursors: Synthetic Scope and Mechanistic Studies
The direct [2 + 2]-photocycloaddition of (Z)-2-phenyl-4-aryliden-5(4H)-oxazolones 1 to give 1,3-diaminotruxillic cyclobutane derivatives 2 in very good yields (75–100%) is reported. The reactionExpand
Muscarinic Acetylcholine Receptors in the Central Nervous System: Structure, Function, and Pharmacology
TLDR
This chapter provides an overview of current knowledge regarding the structure, function, and pharmacology of the mAChRs, with a particular emphasis on their roles in the CNS. Expand
Analysis of equilibrium binding of an orthosteric tracer and two allosteric modulators
TLDR
This paper provides a theoretical basis for analysis of the possibility of having two allosteric modulators interact with the same or different sites on the receptor, and modelled binding of two molecules of one allosterics modulator to one receptor. Expand
...
1
2
...

References

SHOWING 1-10 OF 46 REFERENCES
Protection by Alcuronium of Muscarinic Receptors Against Chemical Inactivation and Location of the Allosteric Binding Site for Alcuronium
TLDR
The effect of alcuronium indicates that the drug interferes with the access of chemical modifiers to the muscarinic sites, and appears to be best explained on the assumption that theDrug binds in close vicinity of the “classical” musCarinic site and sterically blocks the access to this site. Expand
Allosteric effect on muscarinic M2-receptors of derivatives of the alkane-bis-ammonium compound W84: comparison with bispyridinium-type allosteric modulators
Abstract The symmetrically shaped W84 = N,N,N′,N′-tetramethyl-N,N′-bis-(3-phthalimido-propyl)-N,N′-hexane-1,6-diyl-bis-ammonium dibromide is a potent allosteric stabilizer of antagonist-binding toExpand
M2 receptor binding of the selective antagonist AF-DX 384: possible involvement of the common allosteric site.
TLDR
The hypothesis was tested that M2-selective antagonists partially utilize the allosteric site of muscarinic M2 receptors and the results suggest that the binding domain of AF-DX 384 partially overlaps with the common allosterics site of the M2 receptor protein. Expand
Molecular rigidity and potency of bispyridinium type allosteric modulators at muscarinic M2-receptors.
TLDR
The aromatic moiety of non-symmetric bispyridinium-type modulators does not seem to be part of the pharmacophore involved in the inhibitory effect on the association of [3H]NMS, and a rigid aromatic lateral moiety appears to be essential for the interaction with the recognition site mediating the allosteric delay of [ 3H?]NMS dissociation from muscarinic M2-receptors. Expand
Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies.
TLDR
The results demonstrate the potential for developing allosteric enhancers of acetylcholine affinity at individual subtypes of muscarinic receptor and suggest that minor modification of a compound showing positive, neutral, or low negative cooperativity with acetyl choline may yield compounds with various patterns of cooperativity across the receptor subtypes. Expand
Modulation of the structure‐binding relationships of antagonists for muscarinic acetylcholine receptor subtypes
TLDR
The ability to produce enhanced or attenuated affinities and selectivities of antagonists, resulting from the induction of different conformations of the receptor by a variety of physical, chemical or molecular biological perturbations may lead to a better understanding of the structural basis of drug receptor interactions. Expand
Two populations of muscarinic binding sites in the chick heart distinguished by affinities for ligands and selective inactivation
TLDR
It is proposed that the major population of binding sites with high affinities for AF‐DX116 and methoctramine and the lower affinity for pirenzepine represents the M2‐like receptors, while the minor population represents the N‐[3H‐methyl]‐scopolamine‐related receptors. Expand
Identification of drugs competing with d-tubocurarine for an allosteric site on cardiac muscarinic receptors.
TLDR
To identify the compounds that preferentially recognize this accessory site (as opposed to the classical muscarinic binding site), it is likely that methoctramine and pentamethylene-bis(4-diphenylacetoxymethylpiperidine)bromide had comparable affinities for theMuscarinic site and the accessory site. Expand
Subtype selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors.
TLDR
Differences between the effects of alcuronium on individual muscarinic receptor subtypes are apparently responsible for differences between the allosteric effects ofAlcur onium on mus carinic receptors in various tissues that had been described previously. Expand
Positive allosteric interactions on cardiac muscarinic receptors: effects of chemical modifications of disulphide and carboxyl groups.
TLDR
The results suggest that the disulphide bridge connecting the first two extracellular loops of muscarinic receptors is important for the positive allosteric action of alcuronium and that three carboxyl groups (presumably aspartate residues) are involved in receptor interactions with alcur onium and methyl-N-scopolamine. Expand
...
1
2
3
4
5
...