Abstract
The analgesic properties of the tropane analogue (+/-)-SM 21 have been attributed to the antagonism of presynaptic m2 receptors resulting in a potentiation of acetylcholine release. However, drugs targeting a number of other neurotransmitter receptors have been shown to enhance acetylcholine release. In the current study, in vitro studies were conducted in order to determine the affinity of (+/-)-SM 21 for serotonin 5-HT3, 5-HT4, and sigma receptors. Our results indicate that (+/-)-SM 21, and its structural congeners, have a relatively high affinity for sigma2 receptors relative to their reported affinity for muscarinic receptors. The higher affinity for sigma2 versus sigma1 receptors indicates that (+/-)-SM 21 may be a suitable lead compound for developing sigma2-selective ligands.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / chemistry
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Analgesics / metabolism*
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Animals
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Atropine / chemistry
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Atropine / metabolism
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Benzimidazoles / chemistry
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Benzimidazoles / metabolism
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Benztropine / chemistry
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Benztropine / metabolism
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Binding, Competitive
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Brain / metabolism*
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / metabolism
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Butyrates / chemistry
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Butyrates / metabolism*
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Guinea Pigs
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In Vitro Techniques
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Ligands
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Muscarinic Antagonists / chemistry
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Muscarinic Antagonists / metabolism
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Rats
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Receptors, Serotonin / metabolism
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Receptors, Serotonin, 5-HT3
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Receptors, Serotonin, 5-HT4
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Receptors, sigma / metabolism*
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Serotonin Antagonists / chemistry
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Serotonin Antagonists / metabolism
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Sigma-1 Receptor
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Structure-Activity Relationship
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Tropanes / chemistry
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Tropanes / metabolism*
Substances
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Analgesics
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Benzimidazoles
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Bridged Bicyclo Compounds, Heterocyclic
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Butyrates
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Ligands
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Muscarinic Antagonists
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT3
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Receptors, sigma
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Serotonin Antagonists
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Tropanes
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sigma-2 receptor
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(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide
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SM 21
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Receptors, Serotonin, 5-HT4
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Benztropine
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Atropine
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bemesetron