Cyclic derivatives of morphiceptin possess anti-transit effect in the gastrointestinal tract and alleviate abdominal pain in mice

• DOI: 10.1007/s43440-020-00084-4
• Publication Date: 2020-03-03T14:02:48Z
• Authors: Agata Szymaszkiewicz; Jakub Włodarczyk; Marzena Mazur; Jacek Olczak; Jakub Fichna; Marta Zielińska
• Keywords: Pharmacotherapy; Gastrointestinal transit

Irritable bowel syndrome (IBS) is a chronic condition with recurring gastrointestinal (GI) symptoms: altered motility and abdominal pain. As endogenous opioid system participates in pain perception the control of GI peristalsis, opioids have been proposed as promising therapy IBS. In previous study, we observed that morphiceptin derivative, P-317 (Dmt-cyclo-(D-Lys-Phe-D-Pro-Asp)-NH2), presents features to be applied this project, tested whether modifications cyclic morphiceptin-based structure: fluorination (compound 1) or peptide bond reduction 2) improve pharmacological effect. We evaluated derivatives mouse under physiological (GI transit) pathophysiological (castor oil diarrhea, stress-induced hypermotility, visceral pain) conditions. Both compounds prolonged transit. Compound 1 inhibited upper transit colon; compound 2 remained inactive. hypermotility stressed mice delayed acute diarrhea comparison control. Only exerted antinociceptive None derivatives, similar P-317, affected locomotor activity. equally effective tract. The decreased activity 2. Fluorination appears an efficient way increase effects analogs