A highly selective κ-opioid receptor agonist with low addictive potential and dependence liability

Buprenorphine analogs have been synthesized. In the studies of analgesic and addictive effects in mice and [35S]GTPγS binding assay in human brain tissue, an analog of buprenorphine where the tert-butyl is replaced by a cyclobutyl moiety (16) has been identified as a selective κ-partial agonist which gives antinociceptive effects, but has low abuse potential. The results may lead to lower degrees of dysphoria than full κ-agonists.

Graphical abstractBuprenorphine analogs were synthesized. In the studies of analgesic and addictive effects in mice and [35S]GTPγS binding assay in human brain tissue 16, was identified as a selective κ-partial agonist lacking abuse potential.Figure optionsDownload full-size imageDownload as PowerPoint slide