Novel Treatment of Irritable Bowel Syndrome (IBS) and Other Disorders of the Peripheral Nervous System Using Peripherally Restricted Positive Allosteric Modulators of GABA‑A Receptor.

The invention in this patent application relates to 6,9-dihydro-5H-imidazo-[1,2-a]-[1,4]-diazepine derivatives (or their N-oxides) represented herein by formula 1. These compounds are peripherally restricted, positive allosteric modulators of one or more GABA-A receptors. They selectively target the peripheral nervous system and body organs and do not substantially penetrate the blood-brain barrier. Thus, they may provide useful treatment for irritable bowel syndrome and other related peripheral disorders, including, but not limited to, functional abdominal pain, chronic idiopathic diarrhea, visceral pain syndromes, inflammatory bowel diseases, bile acid malabsorption, and drug-induced gastrointestinal dysmotility.