Abstract
The extensive role of the endocannabinoid system in homeostatic regulation and the fact that G protein-coupled receptors (GPCRs) are the most common drug targets makes the cannabinoid receptor 1 (CB1) a suitable subject for development of novel therapeutics.
Recently, research on CB1-targeting drugs has shifted to allosteric modulators in the hope that they offer fewer adverse effects than orthosteric ligands. Allosteric binding sites are distinct from orthosteric sites and are less conserved in comparison, allowing allosteric ligands to exhibit a greater receptor selectivity. In contrast to promising in vitro studies, the existing allosteric modulators such as ORG27569 have not demonstrated substantial activity in vivo. ABM300, a novel allosteric modulator has been shown to alleviate abnormal behaviours in hyperdopaminergic mice models. We aimed to characterise ABM300 in vitro (in HEK293 cells), in comparison with ORG27569.