Abstract
Structural elaboration of phenylethylamine to 9-(aminomethyl)-9,10-dihydroanthracene (AMDA) produces an agent with high affinity (Ki = 9.5-21 nM) at 5-HT2A receptors. It was shown that AMDA acts as a 5-HT2A receptor antagonist. The structure and molecular geometry of AMDA are not consistent with existing pharmacophore models for 5-HT2A receptor antagonist activity. Thus, AMDA may be a structurally novel parent of a new class of 5-HT2A receptor antagonists that binds to the receptor in a unique fashion that is distinct from the binding topology of existing 5-HT2A receptor antagonists.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Anthracenes / chemistry
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Anthracenes / metabolism*
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Binding, Competitive
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Ketanserin / metabolism
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Mice
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Phenols / metabolism
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Phosphatidylinositols / metabolism
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Propane / analogs & derivatives
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Propane / metabolism
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Radioligand Assay
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / chemistry
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Serotonin Antagonists / metabolism*
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Structure-Activity Relationship
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Tritium
Substances
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1,2,5-dimethoxy-4-bromophenol-2-aminopropane
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9-(aminomethyl)-9,10-dihydroanthracene
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Anthracenes
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Phenols
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Phosphatidylinositols
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin
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Serotonin Antagonists
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Tritium
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Ketanserin
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Propane