Abstract
In search of a backup M(2) muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models. The improvement of oral efficacy was achieved by modulating both the molecular weight and lipophilicity of the lead compounds.
MeSH terms
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Acetylcholine / metabolism
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Administration, Oral
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Animals
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Autoreceptors / antagonists & inhibitors*
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Avoidance Learning / drug effects
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Central Nervous System Agents / chemical synthesis*
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Central Nervous System Agents / chemistry
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Central Nervous System Agents / pharmacology
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Corpus Striatum / metabolism
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Humans
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In Vitro Techniques
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Microdialysis
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Molecular Conformation
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Muscarinic Antagonists / chemical synthesis*
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Muscarinic Antagonists / chemistry
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Muscarinic Antagonists / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Rats
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Receptor, Muscarinic M2
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Receptors, Muscarinic / drug effects*
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Structure-Activity Relationship
Substances
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Autoreceptors
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Central Nervous System Agents
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Muscarinic Antagonists
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Piperidines
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Receptor, Muscarinic M2
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Receptors, Muscarinic
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Acetylcholine