Abstract
To acquire more information about the so-called "muscarinic subsite", compound 4 was synthesized and tested. The results show that in comparison with deoxamuscarine (23) the muscarinic potency of 4 on M2 and M3 subtypes is not significantly altered by the presence of an epoxidic function, which confirms the donor-acceptor hydrogen bonding character of this receptive site. Conversely, there is a negative influence on the transduction processes. In addition, a second hydroxylic function bound on the carbon carrying the terminal methyl of the fourth substituent on the nitrogen dramatically affects the muscarinic behavior; the resulting compounds (11-14) lack any agonist or antagonist activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic*
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Guinea Pigs
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In Vitro Techniques
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Male
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Parasympathomimetics / chemical synthesis*
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Parasympathomimetics / pharmacology
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Quaternary Ammonium Compounds / chemical synthesis*
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Quaternary Ammonium Compounds / pharmacology
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Receptors, Muscarinic / drug effects
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Bridged Bicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Parasympathomimetics
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Quaternary Ammonium Compounds
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Receptors, Muscarinic
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trimethyl(1-methyl-6-oxabicyclo(3.1.0)hex-3-yl)methylammonium