@article{WaelbroeckCamusTastenoyetal.1994, author = {Waelbroeck, M. and Camus, J. and Tastenoy, M. and Feifel, R. and Mutschler, E. and Tacke, R. and Strohmann, C. and Rafeiner, K. and Rodrigues de Miranda, J. F. and Lambrecht, G.}, title = {Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor suhtypes}, series = {British Journal of Pharmacology}, volume = {112}, journal = {British Journal of Pharmacology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128265}, pages = {505-514}, year = {1994}, abstract = {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) 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.}, language = {en} } @article{TackeRafeinerStrohmannetal.1989, author = {Tacke, Reinhold and Rafeiner, K. and Strohmann, C. and Mutschler, E. and Lambrecht, G.}, title = {Synthesis of the selective antimuscarinic agent 4-{[cyclohexylhydroxy(2-methoxyphenyl)silyl]methyl}-1,1-dimethylpiperazinium methyl sulfate (o-methoxy-sila-hexocyclium methyl sulfate)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63930}, year = {1989}, abstract = {The synthesis of the potent and highly selective silicon-containing antimuscarinic agent o-methoxysila- hexocyclium methyl sulfate and its corresponding tertiary amine (isolated as the dihydrochloride) is described. The quarternary compound is an omethoxy derivative of sila-hexocyclium methyl sulfate, which represents one of the tools currently used in experimental pharmacology for the subclassification of muscarinic receptors. The omethoxy derivative, the pharmacological profile of which differs substantially from tbat of the nonmethoxy compound, is also recommended as a tool for the investigation of muscarinic receptor heterogeneity.}, subject = {Anorganische Chemie}, language = {en} }