Eric Sparkes, Axelle Timmerman, Jack W Markham, Rochelle Boyd, Rebecca Gordon, Katelyn A Walker, Richard C Kevin, David E Hibbs, Samuel D Banister, Elizabeth A Cairns, Christophe Stove, Adam Ametovski
ADB-HEXINACA has been recently reported as a synthetic cannabinoid receptor agonist (SCRA), one of the largest classes of new psychoactive substances (NPSs). This compound marks the entry of the n -hexyl tail group into the SCRA landscape, which has continued in the market with recent, newly detected SCRAs. As such, a proactive characterization campaign was undertaken, including the synthesis, characterization, and pharmacological evaluation of ADB-HEXINACA and a library of 41 closely related analogues. Two in vitro functional assays were employed to assess activity at CB1 and CB2 cannabinoid receptors, measuring Gβγ -coupled agonism through a fluorescence-based membrane potential assay (MPA) and β-arrestin 2 (βarr2) recruitment via a live cell-based nanoluciferase complementation reporter assay...
April 10, 2024: ACS Chemical Neuroscience