Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from muco- chloric acid and were optimised as CCK selective ligands using radiolabelled binding assays. Apotent CCK1 selective ligand was identified ( PNB-081: CCK1=20nM) as part of systematic SAR optimisation. The antagonism was confirmed for the ligands by using isolated tissue preparations with CCK8S. The cholecystokinin antagonist PNB-081 potentiated the analgesic effect of morphine and reversed opiate tolerance in mice from doses >1 mg/kg by oral administration.