Peripheral CB1 Receptor Antagonist for Therapeutic Use in Metabolic Syndrome

National Center For Advancing Translational Sciences

Investigators

Abstract

Recent clinical studies have demonstrated the potential efficacy of compounds that block the type1 cannabinoid (CB1) receptor for treating obesity and its metabolic complications. Unfortunately, these compounds also elicited depression and anxiety, making them unsuitable for therapeutic use. Studies in animal models of obesity have indicated that the beneficial metabolic effects of CB1 receptor blocking drugs is mediated, at least in part, by blockade of CB1 receptors in peripheral tissues, including the liver, fat and skeletal muscle cells, whereas their neuropsychiatric side effects are due to blockage of CB1 receptors in the brain. The investigators modified the chemical structure of currently available CB1-blocking drugs in a way that reduced their ability to penetrate the blood-brain barrier, but that did not affect their oral bioavailability, selectivity and high affinity for the CB1 receptor. The BrIDGs team completed the following studies on JD3057: - Formulation development - Manufacture of drug product to support Phase I studies - Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies - Investigational New Drug (IND)-directed toxicology