Binding and functional properties of antimuscarinics of the hexocyclium/sila-hexocyclium and hexahydro-diphenidol/hexahydro-sila-diphenidol type to muscarinic receptor subtypes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-63944
- l In an attempt to assess the structural requirements for the musearlnie receptor selectivity of hexahydro-diphenidol (hexahydro-difenidol) and hexahydro-sila-diphenidol (hexahydro-sila-difenidol), a serles of structurally related C/Si pairs were investigated, along with atropine, pirenzepine and methoctramine, for their binding affinities in NB-OK 1 cells as well as in rat heart and pancreas. 2 The action of these antagonists at musearlnie receptors mediating negative inotropic responses in guinea-pig atrla and ileal contractions has also beenl In an attempt to assess the structural requirements for the musearlnie receptor selectivity of hexahydro-diphenidol (hexahydro-difenidol) and hexahydro-sila-diphenidol (hexahydro-sila-difenidol), a serles of structurally related C/Si pairs were investigated, along with atropine, pirenzepine and methoctramine, for their binding affinities in NB-OK 1 cells as well as in rat heart and pancreas. 2 The action of these antagonists at musearlnie receptors mediating negative inotropic responses in guinea-pig atrla and ileal contractions has also been assessed. 3 Antagonist binding data indicated that NB-OK 1 cells (M\(_1\) type) as weil as rat heart (cardiac type) and pancreas (glandularjsmooth muscle type) possess different muscarinic receptor subtypes. 4 A highly significant correlation was found between the binding affinities of the antagonists to muscarinic receptors in rat heart and pancreas, respectively, and the affinities to muscarinic receptors in guinea-pig atria and ileum. This implies that the musearlnie binding sites in rat heart and the receptors in guinea-pig atrla are essentially similar, but different from those in pancreas and ileum. 5 The antimuscarinic potency of hexahydro-diphenidol and hexahydro-sila-diphenidol at the three subtypes was inftuenced differently by structural modifications (e.g. quaternization). Different selectivity profiles for the antagonists were obtained, which makes these compounds useful tools to investigate further muscarinic receptor heterogeneity. lndeed, the tertiary analogues hexahydrodiphenidol (HHD) and hexahydro-sila-diphenidol (HHSiD) bad an M\(_1\) = glandularjsmooth muscle > cardiac selectivity profile, whereas the quaternary analogues HHD methiodide and HHSiD methiodide were M\(_1\) preferring (M\(_1\) > glandularjsmooth muscle, cardiac).…
Author: | M. Waelbroeck, M. Tastenoy, J. Camus, J. Christophe, C. Strohmann, H. Linoh, H. Zilch, Reinhold Tacke, E. Mutschler, G. Lambrecht |
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URN: | urn:nbn:de:bvb:20-opus-63944 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Anorganische Chemie |
Language: | English |
Year of Completion: | 1989 |
Source: | British journal of pharmacology (1989) 98, 1, 197-205. |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
GND Keyword: | Anorganische Chemie |
Release Date: | 2012/02/17 |
Licence (German): | Deutsches Urheberrecht |