Abstract:
:The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric therapeutic compounds, which target the endogenous ligand-binding site of CB1, has been challenging due to detrimental side effects including psychoactivity, depression, and suicidal thoughts. However, CB1 also has an allosteric binding site(s), which is topographically distinct from the orthosteric site. Allosteric modulation of CB1 has a number of potential advantages including providing a mechanism for more precise control of downstream pathways and circumventing these side effects. In this review, we summarize the concept of allosteric modulation and focus on the structure-activity relationship studies of the well-characterized allosteric modulators, ORG27569 and PSNCBAM-1 and their derivatives, and a few other recent modulators. We review studies on the properties of these modulators on CB1 signaling in cells and their effects in vivo. While many current allosteric modulators also produce complex outcomes, they provide new advances for the design of CB1 centered therapeutics.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Dopart R,Lu D,Lichtman AH,Kendall DAdoi
10.1080/03602532.2018.1428342subject
Has Abstractpub_date
2018-02-01 00:00:00pages
3-13issue
1eissn
0360-2532issn
1097-9883journal_volume
50pub_type
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