Abstract
Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M(1), M(2), and M(4) receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Benzilates / antagonists & inhibitors
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Benzilates / chemistry
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Binding, Competitive
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CHO Cells
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Carbachol / pharmacology
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Cell Line
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Colforsin / antagonists & inhibitors
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Colforsin / pharmacology
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Cricetinae
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Cyclic AMP / metabolism
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Humans
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Hypothermia / chemically induced
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Male
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Mice
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Models, Molecular
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Muscarinic Agonists / chemical synthesis*
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Muscarinic Agonists / metabolism
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Muscarinic Agonists / pharmacology*
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Nervous System Diseases / drug therapy*
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / metabolism
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Pyridines / pharmacology*
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Radioligand Assay
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Rats
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Rats, Long-Evans
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Receptors, Muscarinic / metabolism
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Thiadiazoles / chemical synthesis*
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Thiadiazoles / chemistry
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Thiadiazoles / metabolism
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Thiadiazoles / pharmacology*
Substances
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Benzilates
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Muscarinic Agonists
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Pyridines
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Receptors, Muscarinic
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Thiadiazoles
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Colforsin
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Carbachol
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Cyclic AMP