ABSTRACT
Background: Opioid analgesics, which are classifi ed as μ-opioid receptor agonists, are known to induce spasms or contraction of the sphincter of Oddi (SO), thereby inducing or exacerbating biliary diseases such as biliary obstruction, gallbladder dysfunction, cholelithiasis, pancreatitis, biliary dyskinesia, cholangitis, and cholecystitis. However, effects of κ-opioid receptor agonists on SO contraction have not been clarifi ed. In the present study, we investigated the effect of nalfurafi ne hydrochloride (nalfurafi ne), (E)-N-[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3- (furan-3-yl)-N-methylprop-2-enamide monohydrochloride, a selective κ-opioid receptor agonist, on spontaneous contraction of rabbit SO. Methods: SO contraction was measured using manometry in anesthetized rabbits. Rabbits were anesthetized with intravenous administration of 25 mg/kg sodium pentobarbital. An open tip catheter was inserted into the common bile duct toward the SO ampullae. Saline was perfused through the lumen of the open tip catheter at a constant rate of 6 ml/hr using a syringe pump. Nalfurafi ne, morphine, and pentazocine were intravenously (i.v.) administered and perfusion pressure was recorded. Results: Morphine (0.3 mg/kg, i.v.) and pentazocine (3 mg/kg, i.v.) were found to increase SO perfusion pressure, suggesting that these opioid analgesics may cause SO contraction. In contrast, nalfurafi ne (0.2 μg/kg, i.v.) decreased the perfusion pressure, indicating that this κ-opioid receptor agonist suppresses SO contraction. Conclusions: These fi ndings suggest that nalfurafi ne is unlikely to induce or exacerbate biliary diseases and may be safely used in patients with these disorders.