TM38837

TM38837 is a peripherally restricted small molecule that acts as an inverse agonist and antagonist of the cannabinoid CB1 receptor. Developed by 7TM Pharma, it was engineered to address the significant central nervous system (CNS) side effects, such as anxiety and depression, that led to the withdrawal of first-generation CB1 blockers like rimonabant. By limiting blood-brain barrier penetration, TM38837 selectively targets peripheral CB1 receptors located in tissues such as the liver, adipose tissue, and skeletal muscle. This peripheral selectivity allows the drug to maintain metabolic benefits, including weight loss and improved glucose homeostasis, while minimizing psychiatric risks. It was the first peripherally restricted CB1 antagonist to enter human clinical trials, with potential applications in obesity, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH).