Abstract
A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M(1), M(2), and M(3) muscarinic receptors using [(3)H] pirenzepine and [(3)H] NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 5 l and 6 i good M(1) and M(3) antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.
MeSH terms
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Animals
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Atropine / pharmacology
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Binding, Competitive
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Cholinergic Agents / chemical synthesis*
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Cholinergic Agents / chemistry
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Cholinergic Agents / pharmacology
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Guinea Pigs
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Ileum / drug effects
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In Vitro Techniques
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Ligands
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Male
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Muscarinic Agonists / pharmacology
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Muscarinic Antagonists / pharmacology
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Organ Specificity
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Oxotremorine / pharmacology
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Rabbits
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Receptors, Muscarinic / drug effects*
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Structure-Activity Relationship
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Swine
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
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Urinary Bladder / drug effects
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Vas Deferens / drug effects
Substances
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Cholinergic Agents
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Ligands
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Muscarinic Agonists
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Muscarinic Antagonists
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Pyrazoles
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Pyridines
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Receptors, Muscarinic
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Triazoles
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Oxotremorine
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Atropine