Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms

Background 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). methods 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. results 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 5 mg/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. conclusion biphalin is an interesting template for novel opioid-based agents to be used in therapy of functional gi diseases. © 2015 institute of pharmacology,polish academy of sciences.