LI-633

LI-633 is a novel, peripherally restricted, benzodiazepine-derived positive allosteric modulator (PAM) of gamma-aminobutyric acid type A (GABA-A) receptors. Developed by the Lieber Institute for Brain Development in collaboration with researchers from the Mayo Clinic and Johns Hopkins University, LI-633 is engineered to potentiate α1, α2, α3, and α5-containing GABA-A receptors while avoiding central nervous system (CNS) penetration. By targeting peripheral GABA-A receptors on sensory pathways connected to the gut, such as dorsal root ganglion (DRG) neurons, LI-633 reduces neuronal excitability and visceral hypersensitivity. In preclinical models, it has demonstrated efficacy in alleviating visceral pain and diarrhea associated with irritable bowel syndrome (IBS) and functional dyspepsia (FD) without causing central side effects like sedation.

Other names

Li633Li-633Li 633