Structural mechanism of CB₁R binding to peripheral and biased inverse agonists.

ABSTRACT: The cannabinoid receptor 1 (CB₁R) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CB₁R antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted their further therapeutic development. The peripherally restricted CB₁R inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CB₁R inhibitors while sparing the negative psychiatric effects. To understand the mechanism of binding and inhibition of CB₁R by peripheral

SUBMITTER: Kumari P 

PROVIDER: S-EPMC11655885 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature