2-NAPHTHALENESULPHONYL L-ASPARTYL-(2-PHENETHYL)AMIDE (2-NAP) - A SELECTIVE CHOLECYSTOKININ CCK(A)-RECEPTOR ANTAGONIST

1 The in vitro pharmacological characterization of the sodium salt of 2-naphthalenesulphonyl 1-aspartyl-(2-phenethyl)amide [2-NAP], a hydrophilic compound derived from the C-terminal aspartate-phenylalanine dipeptide of cholecystokinin (CCK), is described. 2 2-NAP behaved as a competitive antagonist of sulphated cholecystokinin octapeptide (CCK-8) at CCK(A)-receptors in both intact tissue bioassays (guinea-pig gall bladder, pancreas and ileum, human and rabbit gall bladder) and a radioligand displacement assay (guinea-pig pancreatic cells). The mean pK(B), over assays, was 6.5. 3 Compared to the other assays, the rabbit gall bladder assay gave a significantly higher pK(B) estimate [7.01 for 2-NAP and a significantly lower estimate [8.9] for devazepide (formerly L-364,718 and MK-329), a well-characterized CCK(A)-receptor antagonist; these anomalous results suggest that a different class of CCK(A)-receptors may be involved. 4 2-NAP, was found to be highly selective, having at least 300 fold greater affinity for CCK(A)-receptors than for 50 other pharmacological loci, including gastrin/CCK(B), as estimated by bioassay or radioligand displacement.