Abstract
Three series of new N-substituted 1,2,3,4-tetrahydroisoquinolines with 2-, 3-, and 4-membered alkyl chains (a, b, and c, respectively) were synthesized, and the effect of some structural modifications on their 5-HT1A receptor affinities and functional properties was discussed. It was found that the volume of the terminal amide substituent was a crucial parameter which determined 5-HT1A receptor affinities of the tested compounds, while the in vivo activity seemed to depend on both the R-volume and the length of a hydrocarbon chain. It was demonstrated that the most active ligands behaved like agonists or partial agonists at postsynaptic 5-HT1A receptors.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Uptake Inhibitors / pharmacology
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Animals
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Behavior, Animal / drug effects
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Body Temperature / drug effects
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Dose-Response Relationship, Drug
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Isoquinolines / administration & dosage
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Isoquinolines / chemical synthesis*
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Kinetics
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Lip / drug effects
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Magnetic Resonance Spectroscopy
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Male
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Mice
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Models, Chemical
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Protein Binding
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Rats
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Rats, Wistar
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Receptors, Serotonin / chemistry*
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Receptors, Serotonin / classification
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Reserpine / pharmacology
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Tetrahydroisoquinolines*
Substances
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Adrenergic Uptake Inhibitors
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Isoquinolines
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Receptors, Serotonin
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Tetrahydroisoquinolines
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1,2,3,4-tetrahydroisoquinoline
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Reserpine