TY  - JOUR
A1  - Volpato, Daniela
A1  - Holzgrabe, Ulrike
T1  - Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer’s Disease
JF  - Molecules
N2  - The cholinergic hypothesis has been reported first being the cause of memory dysfunction in the Alzheimer’s disease. Researchers around the globe have focused their attention on understanding the mechanisms of how this complicated system contributes to processes such as learning, memory, disorientation, linguistic problems, and behavioral issues in the indicated chronic neurodegenerative disease. The present review reports recent updates in hybrid molecule design as a strategy for selectively addressing multiple target proteins involved in Alzheimer’s disease (AD) and the study of their therapeutic relevance. The rationale and the design of the bifunctional compounds will be discussed in order to understand their potential as tools to investigate the role of the cholinergic system in AD.
KW  - AChE inhibitor
KW  - Alzheimer’s disease
KW  - bitopic ligand
KW  - cholinergic system
KW  - hybrid molecules
KW  - muscarinic receptors
KW  - nicotinic receptors
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197555
SN  - 1420-3049
VL  - 23
IS  - 12
ER  - 
TY  - JOUR
A1  - Pfeiffer, A.
A1  - Rochlitz, H.
A1  - Noelke, B.
A1  - Tacke, R.
A1  - Moser, U.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type
JF  - Gastroenterology
N2  - Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.
KW  - hexahydrosiladifenidol
KW  - muscarinic receptors
KW  - parasympatholytics
KW  - radioligand assay
KW  - parasympatholytics/pharmacology
KW  - gastric acid/secretion
KW  - animals
KW  - piperidines/pharmacology
KW  - piperazines/pharmacology
KW  - gastric/secretion parietal cells
KW  - muscarinic/physiology receptors
KW  - muscarinic/drug effects receptors
KW  - rats
KW  - piperidines
KW  - piperazines
KW  - silahexocyclium
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128337
VL  - 98
IS  - 1
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Kropfgans, Martin
A1  - Tafel, Andrea
A1  - Wiesenberger, Frank
A1  - Sheldrick, William S.
A1  - Mutschler, Ernst
A1  - Egerer, Hansjörg
A1  - Rettenmayr, Nikola
A1  - Gross, Jan
A1  - Waelbroeck, Magali
A1  - Lambrecht, Günter
T1  - (Hydroxymethyl)diphenyl(piperidinoalkyl)silane des Typs (HOCH2)(C6H5)2Si(CH2)nNC5H10 (n = 2,3) und deren Methoiodide: Synthese, Struktur und antimuscarinische Eigenschaften
N2  - No abstract available.
KW  - (Hydroxymethyl)diphenyl(piperidinoalkyl)silanes
KW  - Sila-pridinol
KW  - Sila-difenidol
KW  - muscarinic antagonists
KW  - muscarinic receptors
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86904
ER  -