APPARENT AFFINITY AND POTENCY OF BIBP3226, A NONPEPTIDE NEUROPEPTIDE-Y RECEPTOR ANTAGONIST, ON PURPORTED NEUROPEPTIDE-Y Y-1, Y-2 AND Y-3 RECEPTORS

The newly developed, purported non-peptide neuropeptide Y Y-1 receptor antagonist BIBP3226 was evaluated for its potential effect on the recently characterized Y-3 receptor subtype and for its apparent affinity in rat and human brain membrane binding assays using highly selective neuropeptide Y Y-1 and Y-2 radioligands. BIBP3226 potently blocked (pA(2) = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y-1 receptor bioassay and demonstrated nM affinity for y(1)/[I-125][Leu(31),Pro(34)]peptide YY binding sites. In contrast, it failed to antagonize the biological effects of neuropeptide Y in the rat vas deferens (Y-2) and rat colon (Y-3) and did not significantly competed for Y-2/[I-125]peptide YY-(3-36) binding sites in rat and human brain homogenates. Taken together, the results demonstrate further the high potency and selectivity of BIBP3226 for the neuropeptide Y Y-1 receptor by establishing its lack of antagonist activity on the Y-3 subtype.