Signalling profiles of a structurally diverse panel of synthetic cannabinoid receptor agonists.

In this study, we aimed to characterise the signalling profiles of a structurally diverse panel of novel SCRAs at CB1. We compare SCRAs to traditional reference cannabinoids CP55,940, WIN55,212-2, and THC. The activity of the SCRAs was assessed in key receptor signalling and regulatory pathways, including cAMP production, translocation of β-arrestin 1 and 2, and receptor internalisation. The activity profiles of the ligands were also evaluated using operational analysis to identify ligand bias. Results revealed that SCRAs activities were relatively balanced in the pathways evaluated (compared to WIN55,212-2), although 5F-CUMYL-P7AICA and XLR-11 possessed partial efficacy in cAMP stimulation and β-arrestin translocation. Notably, the SCRAs showed distinct potency and efficacy profiles compared to THC. In particular, while the majority of SCRAs demonstrated robust β-arrestin translocation, cAMP stimulation, and internalisation, THC failed to elicit high efficacy responses in any of these assays. Further study is required to delineate if these pathways could contribute to SCRA toxicity in humans. PMID: 32088263 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research