BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist

• Published in: European journal of pharmacology Vol. 384; no. 2-3; pp. R3 - R5
• Main Authors: Doods, H, Gaida, W, Wieland, H A, Dollinger, H, Schnorrenberg, G, Esser, F, Engel, W, Eberlein, W, Rudolf, K
• Format: Journal Article
• Language: English
• Published: Netherlands 19.11.1999
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - metabolism; Arginine - pharmacology; Benzazepines - metabolism; Benzazepines - pharmacology; Binding, Competitive - drug effects; Cell Line; CHO Cells; Cricetinae; Dose-Response Relationship, Drug; Humans; Iodine Radioisotopes; Male; Muscle Contraction - drug effects; Neuropeptide Y - metabolism; Neuropeptide Y - pharmacology; Radioligand Assay; Rats; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - metabolism; Tumor Cells, Cultured; Vas Deferens - drug effects; Vas Deferens - physiology
• ISSN: 0014-2999

The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [125I]neuropeptide Y with high affinity (IC(50)=3.3 nM) from the human neuropeptide Y Y(2) receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y(2) receptor antagonist.