biphalin and Diarrhea

Opioid receptors play a crucial role in the maintenance of homeostasis in the gastrointestinal (GI) tract. The aim of this study was to characterize the effect of biphalin, a mixed MOP/DOP agonist, on mouse intestinal contractility in vitro and GI motility in vivo and in animal models mimicking symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D).. The effect of biphalin on muscle contractility in vitro was characterized in the ileum and colon. The anti-transit activity of biphalin in vivo was assessed in the following tests: whole gastrointestinal transit, colonic bead expulsion, fecal pellet output and castor oil-induced diarrhea, alone and in the presence of naloxone, and MOP and DOP antagonists.. In vitro, biphalin (10(-10)-10(-6)M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent, opioid antagonist-reversible manner. In vivo, biphalin at the dose of 5mg/kg ip prolonged the whole GI transit and inhibited colonic bead expulsion. Biphalin reversed hypermotility and exerted anti-diarrheal effect in mouse models mimicking IBS-D symptoms.. Biphalin is an interesting template for novel opioid-based agents to be used in therapy of functional GI diseases.

Topics: Analgesics, Opioid; Animals; Diarrhea; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalins; Gastrointestinal Motility; Irritable Bowel Syndrome; Male; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Receptors, Opioid, delta; Receptors, Opioid, mu; Treatment Outcome