Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes
| ISSN: | 0007-1188 |
|---|---|
| DOI: | 10.1111/j.1476-5381.1994.tb13102.x |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d263ffb2a82615a99aa29233c03f5fdc https://doi.org/10.1111/j.1476-5381.1994.tb13102.x |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....d263ffb2a82615a99aa29233c03f5fdc |
| Autor: | Reinhold Tacke, Carsten Strohmann, Günter Lambrecht, Roland Feifel, Ernst Mutschler, Jean Claude Camus, Magali Waelbroeck, J.F. Rodrigues de Miranda, K. Rafeiner, Michèle Tastenoy |
| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Guinea Pigs Scopolamine Derivatives In Vitro Techniques Biology Piperazines Radioligand Assay Structure-Activity Relationship Vas Deferens Internal medicine Muscarinic acetylcholine receptor Tumor Cells Cultured medicine Animals Humans Rats Wistar Receptor Pharmacology Vas deferens Antagonist Parasympatholytics Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 Pirenzepine Muscarinic acetylcholine receptor M1 N-Methylscopolamine Receptors Muscarinic In vitro Rats medicine.anatomical_structure Endocrinology Cattle Female Rabbits Research Article |
| Zdroj: | British Journal of Pharmacology. 112:505-514 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/j.1476-5381.1994.tb13102.x |
| Popis: | 1. We have compared the binding properties of several hexocyclium and sila-hexocyclium derivatives to muscarinic M1 receptors (in rat brain, human neuroblastoma (NB-OK 1) 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 (M1/M4-like), guinea-pig atria (M2), and guinea-pig ileum (M3) muscarinic receptors. 2. Sila-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 o-methoxy-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 (M1 = M4 > or = M3 > or = M2) had a much lower affinity than sila-hexocyclium for the four receptor subtypes, and discriminated the receptor subtypes more poorly than sila-hexocyclium (M1 = M3 > M4 > M2). This is in marked contrast with the very clear selectivity of o-methoxy-sila-hexocyclium for the prejunctional M1/M4-like heteroreceptors in rabbit vas deferens. 5. The tertiary amines demethyl-hexocyclium, demethyl-sila-hexocyclium and demethyl-o-methoxy-sila-hexocyclium had 10 to 30 fold lower affinities than the corresponding quaternary ammonium derivatives. |
| Databáze: | OpenAIRE |
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