Abstract
A conformationally restricted analogue of mescaline, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed using a 5-HT(2A) receptor homology model. The compound possessed 3-fold higher affinity and potency than and efficacy equal to that of mescaline at the 5-HT(2A) receptor. The new analogue substituted fully for LSD in drug discrimination studies and was 5-fold more potent than mescaline. Resolution of this analogue into its enantiomers corroborated the docking experiments, showing the R-(+) isomer to have higher affinity and potency and to have efficacy similar to that of mescaline at the 5-HT(2A) receptor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Cells, Cultured
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Computer Simulation
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Crystallography, X-Ray
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Discrimination Learning / drug effects
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Hallucinogens / chemical synthesis*
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Hallucinogens / pharmacology
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Indans / chemical synthesis*
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Indans / pharmacology
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Inositol Phosphates / biosynthesis
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Lysergic Acid Diethylamide / pharmacology
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Mescaline / analogs & derivatives*
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Mescaline / chemical synthesis*
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Mescaline / pharmacology
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Methylamines / chemical synthesis*
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Methylamines / pharmacology
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Models, Molecular
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Radioligand Assay
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Rats
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Receptor, Serotonin, 5-HT2A / chemistry*
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Sequence Homology, Amino Acid
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Serotonin 5-HT2 Receptor Agonists*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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C-(4,5,6-trimethoxyindan-1-yl)methanamine
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Hallucinogens
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Indans
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Inositol Phosphates
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Methylamines
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Receptor, Serotonin, 5-HT2A
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Serotonin 5-HT2 Receptor Agonists
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Lysergic Acid Diethylamide
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Mescaline