Fatty acyl amides of endogenous tetrahydroisoquinolines are active at the recombinant human TRPV1 receptor.
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.
O'Dell
David K
DK
The Gill Center for Biomolecular Science, 1101 East Tenth Street, Bloomington, IN 47405, USA.
Rimmerman
Neta
N
Pickens
Sarah R
SR
Walker
J Michael
JM
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000819:agonists / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000737:chemistry*
D000577:Amides; D005227:Fatty Acids; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D044005:Tetrahydroisoquinolines; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium