Assessment of high-efficacy agonism in synthetic cannabinoid receptor agonists containing l-<i>tert</i>-leucinate.

ABSTRACT: Synthetic cannabinoid receptor agonists (SCRAs) represent a class of new psychoactive substances that pose great health risks attributed to their wide-ranging and severe adverse effects. Recent evidence has shown that SCRAs with key moieties can confer superagonism, yet this phenomenon is still not well understood. Here we report structure-activity relationships (SARs) of modular SCRAs contributing to superagonism by comparing eight compounds differing by their head moiety (l-valinate vs. l-tert-leucinate), core moiety (indole vs. indazole), and tail moiety (5-fluoropentyl vs. 4-fluorobenzyl) through different modes of bioluminescence resonance energy transfer (BRET) assays. We found that the l-tert-leucinate head moiety and indazole core moiety conferred superagonism across

SUBMITTER: Lucaj C 

PROVIDER: S-EPMC11507767 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature