Effect of nalfurafi ne hydrochloride on the basal pressure of the sphincter of Oddi in anesthetized rabbits.
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Date
2015-03
Authors
Kobayashi, Ryosuke
Nakao, Kaoru
Yamada, Kiyoshi
Miyamoto, Yohei
Mochizuki, Hidenori
Journal Title
Journal ISSN
Volume Title
Publisher
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.
Description
Keywords
Nalfurafi ne hydrochloride, TRK-820, κ-opioid receptor, Sphincter of Oddi, Biliary disease
Citation
Kobayashi Ryosuke, Nakao Kaoru, Yamada Kiyoshi, Miyamoto Yohei, Mochizuki Hidenori. Effect of nalfurafi ne hydrochloride on the basal pressure of the sphincter of Oddi in anesthetized rabbits. International Journal of Basic & Clinical Pharmacology. 2015 Mar-Apr; 4(2): 198-202.