Novel radiolabeled vanilloid with enhanced specificity for human transient receptor potential vanilloid 1(TRPV1)

Abstract

Transient receptor potential vanilloid 1 (TRPV1) has emerged as a promising therapeutic target. While radiolabeled resiniferatoxin (RTX) has provided a powerful tool for characterization of vanilloid binding to TRPV1, TRPV1 shows 20-fold weaker binding to the human TRPV1 than to the rodent TRPV1. We now describe a tritium 13 radiolabeled synthetic vanilloid antagonist, 1-((2-(4-(methyl-[H-3])piperidin-1-yl-4-[H-3])-6-(trifluoromethyl)pyridin-3-yl)-methyl)-3-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)urea ([H-3]MPOU), that embodies improved absolute affinity for human TRPV1 and improved synthetic accessibility.