Abstract
The classical terms agonists and antagonists for G protein coupled receptors (GPCRs) have often become misleading. Even the biased agonism concept does not describe all the possibilities already demonstrated for GPCRs. The cannabinoid CB2 receptor (CB2R) emerged as a promising target for a variety of diseases. Reasons for such huge potential are centered around the way drugs sit in the orthosteric and/or exosites of the receptor. On the one hand, a given drug in a specific CB2R conformation leads to a signaling cascade that differs qualitatively and/or quantitatively from that triggered by another drug. On the other hand, a given drug may lead to different signaling outputs in two different tissues (or cell contexts) in which the conformation of the receptor is affected by allosteric effects derived from interactions with other proteins or with membrane lipids. This highlights the pharmacological complexity of this receptor and the need to further unravel the binding mode of CB2R ligands in order to fine-tune signaling effects and therapeutic propositions.
Highlights
G protein-coupled receptors (GPCRs) are the target of about 40% of current drugs (Hauser et al, 2017)
Functional selectivity is a property of GPCRs that has recently become relevant to overcome the issues related to the lack of success of GPCR-targeted drug candidates (Chang and Bruchas, 2014; Franco et al, 2018)
We aim to review the multiple therapeutic possibilities resulting from targeting the cannabinoid receptor type 2 (CB2R) orthosteric and/ or non-orthosteric sites
Summary
G protein-coupled receptors (GPCRs) are the target of about 40% of current drugs (Hauser et al, 2017). The potential of GPCRs as therapeutic targets is still considered to be high, there have been only a few recent approvals of drugs targeting these receptors. Functional selectivity of a given compound acting on the targeted receptor could achieve the desired effect(s) while minimizing side effects. We aim to review the multiple therapeutic possibilities resulting from targeting the cannabinoid receptor type 2 (CB2R) orthosteric and/ or non-orthosteric sites. CB2R appears as more promising in drug discovery than the cannabinoid receptor type 1 (CB1R) as some of CB1R agonists have psychotropic effects and an antagonist approved for human use (for weight control) was withdrawn due to serious side effects (Christensen et al, 2007; Sam et al, 2011). Safety will not be considered in the present article
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
