Characterization of N,N(Me)2-Dmt-Tic-OH, a delta selective opioid dipeptide antagonist

N,N(Me)(2)-Dimethyl-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-OH (N,N(Me)(2)-Dmt-Tic-OH) is a very selective delta opioid dipeptide with elevated antagonist activity. We have radiolabelled this compound by catalytic tritiation of the N,N(Me)(2)-Dmt(3',5'-I-2)-Tic-OH precursor. The ligand labelled rat brain membranes with a K-d value of 0.42 nM and a B-max of 63.12 fmol/mg protein. The new tritiated ligand showed high affinity for the delta opioid receptor whereas its binding at mu and kappa opioid receptors was weak. N,N(Me)(2)-Dmt-Tic-OH was able to inhibit the agonist-stimulated binding of the non-hydrolysable GTP analogue [S-35]GTP gamma S, thus attenuating the activation of G proteins via opioid receptors. This simple opioid dipeptide in both normal and labelled form may serve as a useful tool to study delta opioid receptors in vitro and in vivo. NeuroReport 11:2083-2086 (C) 2000 Lippincott Williams & Wilkins.