CHARACTERIZATION OF [H-3] CP-96,501 AS A SELECTIVE RADIOLIGAND FOR THE SEROTONIN 5-HT1B RECEPTOR - BINDING-STUDIES IN RAT-BRAIN MEMBRANES

3-(1,2,5,6-Tetrahydro-4-pyridyl)-5-n-propoxyindole (CP-96,501) was found to be a more selective ligand at the serotonin 5-HT1B receptor than the commonly used 5-HT1B agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-methoxyindole (RU 24969). In rat brain membranes, the tritiated derivative, [H-3]CP-96,501, was found to bind with a high affinity (K(D), 0.21 nM) to a single binding site (n(H), 1.0). The receptor density of this site (B(max), 72 fmol/mg of protein) matched that of the 5-HT1B receptor determined with [H-3]5-HT. Competition curves of 16 serotonergic compounds in [H-3]CP-96,501 binding also indicated a single binding site. The rank order of their binding affinities with this new radioligand showed a high degree of correlation with their affinities at the 5-HT1B receptor determined with [H-3]5-HT or [I-125]iodocyanopindolol. Serotonergic compounds displayed competitive inhibition of [H-3]CP-96,501 binding. In the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p], [H-3]CP-96,501 binding was reduced, while the potency of CP-96,501 to displace [I-125]iodocyanopindolol binding was also decreased. These findings are consistent with the agonist nature of CP-96,501. The results of this study suggest that [H-3]CP-96,501 is a useful agonist radioligand for the 5-HT1B receptor.