Abstract
Alkylthio-TZTPs (3-(3-alkylthio-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-met hylpyridines) and corresponding azabicyclic analogs were tested for m1 efficacy in cloned human m1 receptors and for antinociceptive activity in the mouse grid shock assay. The m1 (%PI) SAR were distinctly different from the analgesia and the salivation SAR, suggesting that analgesia is mediated by neither m1 nor M3 muscarinic receptors.
MeSH terms
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Analgesics / chemistry
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Analgesics / pharmacology*
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Animals
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Carbachol / pharmacology
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Dose-Response Relationship, Drug
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Humans
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Inhibitory Concentration 50
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Mice
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Molecular Structure
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Muscarinic Agonists / chemistry
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Muscarinic Agonists / pharmacology*
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Pain Threshold / drug effects
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Pain Threshold / physiology
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Parasympathomimetics / chemistry
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Parasympathomimetics / pharmacology*
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Phosphatidylinositols / metabolism
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Pyridines / chemistry
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Pyridines / pharmacology*
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Receptor, Muscarinic M1
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Receptors, Muscarinic / metabolism*
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Salivation / drug effects
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Structure-Activity Relationship
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Thiadiazoles / chemistry
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Thiadiazoles / pharmacology*
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Vocalization, Animal / drug effects
Substances
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Analgesics
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Muscarinic Agonists
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Parasympathomimetics
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Phosphatidylinositols
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Pyridines
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Receptor, Muscarinic M1
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Receptors, Muscarinic
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Thiadiazoles
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3-(3-(hexylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine
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Carbachol