Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor suhtypes

Please always quote using this URN: urn:nbn:de:bvb:20-opus-128265
  • 1 We have compared the binding properties of several hexocyclium and sila-hexocyclium derivatives to muscarinic Ml receptors (in rat brain, human neuroblastoma (NB-OK I) cells and calf superior cervical ganglia), rat heart M2 receptors, rat pancreas M3 receptors and M4 receptors in rat striatum, with their functional antimuscarinic properties in rabbit vas deferens (Ml/M4-like), guinea-pig atria (M2), and guinea-pig ileum (M3) muscarinic receptors. 2 Si la-substitution (C/Si exchange) of hexocyclium (~ sila-hexocyclium) and1 We have compared the binding properties of several hexocyclium and sila-hexocyclium derivatives to muscarinic Ml receptors (in rat brain, human neuroblastoma (NB-OK I) cells and calf superior cervical ganglia), rat heart M2 receptors, rat pancreas M3 receptors and M4 receptors in rat striatum, with their functional antimuscarinic properties in rabbit vas deferens (Ml/M4-like), guinea-pig atria (M2), and guinea-pig ileum (M3) muscarinic receptors. 2 Si la-substitution (C/Si exchange) of hexocyclium (~ sila-hexocyclium) and demethyl-hexocyclium (~demethyl-sila-hexocyclium) did not significantly affect their affinities for muscarinic receptors. By contrast, sila-substitution of demethoxy-hexocyclium increased its affinity 2 to 3 fold for all the muscarinic receptor subtypes studied. 3 The p-fluoro- and p-chloro-derivatives of sila-hexocyclium had lower affinities than the parent compound at the four receptor subtypes, in binding and pharmacological studies. 4 In binding studies, o-methoxy-sila-hexocyclium (Ml = M4 ~ M3 ~ M2) had a much lower affinity than sila-hexocyclium for the four receptor subtypes, and discriminated the receptor subtypes more poorly than sila-hexocyclium (Ml = M3> M4> M2)' This is in marked contrast with the very clear selectivity of demethoxy-sila-hexocyclium for the prejunctional MtlM4-like heteroreceptors in rabbit vas deferens. 5 The tertiary amines demethyl-hexocyclium, demethyl-sila-hexocyclium and demethyl-o-methoxy-silahexocyclium had 10 to 30 fold lower affinities than the corresponding quaternary ammonium derivatives.show moreshow less

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Metadaten
Author: M. Waelbroeck, J. Camus, M. Tastenoy, R. Feifel, E. Mutschler, R. Tacke, C. Strohmann, K. Rafeiner, J. F. Rodrigues de Miranda, G. Lambrecht
URN:urn:nbn:de:bvb:20-opus-128265
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Anorganische Chemie
Language:English
Parent Title (English):British Journal of Pharmacology
Year of Completion:1994
Volume:112
Pagenumber:505-514
Source:British Journal of Pharmacology (1994), 112, 505-514
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 546 Anorganische Chemie
Tag:Hexocyclium/sila-hexocyclium derivatives; binding/functional correlations; muscarinic receptor antagonists; muscarinic receptor subtypes; o-methoxy-sila-hexocyclium; structure/ affinity relationships
Release Date:2016/03/01
Licence (German):License LogoDeutsches Urheberrecht