Abstract
In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M(2)/M(3) muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M(3) preferring antagonist (±)-17, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Pressure / drug effects
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CHO Cells
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Cricetinae
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Cricetulus
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Crystallography, X-Ray
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Dioxanes / chemical synthesis*
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Dioxanes / chemistry
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Dioxanes / pharmacology
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Guinea Pigs
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Heart Rate / drug effects
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Humans
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Molecular Structure
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Muscle Contraction
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Rats
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Receptor, Muscarinic M3 / agonists
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Receptor, Muscarinic M3 / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Urinary Bladder / drug effects
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Urinary Bladder / physiology
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Urination / drug effects
Substances
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(6,6-diphenyl-1,4-dioxan-2-yl)-N,N-dimethylmethanamine
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Dioxanes
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Receptor, Muscarinic M3
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1,4-dioxane