Abstract
The SAR of capsazepine revealed that tetrahydroisoquinoline (TIQ) moiety is a core pharmacophore of TRPV1 activity. This implied that conjugates of endogenous TIQs with fatty acids would be active at TRPV1 receptors. Six such compounds were synthesized and tested for calcium mobilization at recombinant TRPV1 receptors overexpressed in HEK293 cells. Three compounds showed partial TRPV1 agonism with EC(50) values in the low micromolar range and maximal efficacies between 25% and 55% of capsaicin.
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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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology*
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Calcium / metabolism*
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Capsaicin / analogs & derivatives*
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Capsaicin / pharmacology
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Cells, Cultured
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Fatty Acids / chemical synthesis
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Fatty Acids / chemistry
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Fatty Acids / pharmacology*
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Humans
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Kidney / cytology
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Kidney / drug effects*
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Kidney / metabolism
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Recombinant Proteins / agonists
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Recombinant Proteins / metabolism
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TRPV Cation Channels / agonists*
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TRPV Cation Channels / metabolism
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Tetrahydroisoquinolines / chemistry*
Substances
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Amides
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Fatty Acids
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Recombinant Proteins
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TRPV Cation Channels
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TRPV1 receptor
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Tetrahydroisoquinolines
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capsazepine
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Capsaicin
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Calcium