Ergoline derivatives as highly potent and selective antagonists at the somatostatin sst1 receptor

Abstract Non-peptidic compounds containing the octahydro-indolo[4,3- fg ]quinoline (ergoline) structural element have been optimized into derivatives with high affinity (p K d r sst 1  > 9) and selectivity (>1000-fold for h sst 1 over h sst 2 –h sst 5 ) for the somatostatin sst 1 receptor. In functional assays, these ergolines act as antagonists at human recombinant sst 1 receptors. Pharmacokinetic studies in rodents reveal good oral bioavailability and brain penetration for some of these compounds.