Inhibition of proteases as a novel therapeutic strategy in the treatment of metabolic, inflammatory and functional diseases of the gastrointestinal tract

Activation of the endogenous nociceptin system by selective nociceptin receptor agonist SCH 221510 produces antitransit and antinociceptive effect: a novel strategy for treatment of diarrhea‐predominant IBS

“…The main symptoms of diarrhea‐predominant IBS (IBS‐D) are abdominal pain, loose stool consistency, and increased bowel movement frequency, along with non‐specific GI tract‐related symptoms, such as bloating, feeling of distension, and general discomfort. Endogenous systems, for example opioid and cannabinoid have been proposed as possible sites of action for future anti‐IBS‐D drugs . A number of recent reports suggest that the nociceptin system, which comprises the nociceptin receptors (NOP) and their endogenous peptide ligand nociceptin, plays an important role in the GI system in physiological conditions and could also be implicated in IBS‐D pathophysiology.…”

“…Endogenous systems, for example opioid and cannabinoid have been proposed as possible sites of action for future anti-IBS-D drugs. 2,3 A number of recent reports suggest that the nociceptin system, which comprises the nociceptin receptors (NOP) and their endogenous peptide ligand nociceptin, plays an important role in the GI system in physiological conditions and could also be implicated in IBS-D pathophysiology. NOP are widely distributed in the central (CNS), peripheral, and sensory nervous systems, and in other peripheral tissues, such as rat 4 and porcine 5 intestine, and mouse 6 and human 7,8 immune cells.…”

Encenicline, an 7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice

“…Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC), and Crohn's disease (CD), is a group of chronic and relapsing gastrointestinal (GI) disorders manifested mainly by imbalanced immunologic response leading to an inflammatory state in the gut, disrupted motility, and abdominal pain (Sałaga et al, 2013;Sobczak et al, 2014). Although several pharmacological strategies have been employed to treat IBD, none of them has entirely succeeded.…”

Antinociceptive potency of enkephalins and enkephalinase inhibitors in the mouse model of colorectal distension—proof‐of‐concept

“…[8] The major target of enkephalinase inhibitors is to augment the local levels of endogenous enkephalins, thus, prolonging the binding time to ORs and enhancing OR-dependent effects. Thus, the concept of developing enkephalinase inhibitors as therapeutics appears promising.…”