title: Nalfurafine hydrochloride, a selective κ opioid receptor agonist, has no reinforcing effect on intravenous self-administration in rhesus monkeys.
abstract: Nalfurafine hydrochloride [(E)-N-[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl)-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion). These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Kaoru_Nakao@nts.toray.co.jp.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Hirakata
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kainoh
authors.affiliation: Marketing Department, Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Wakasa
authors.affiliation: Scientific Advisor, Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Tomoji
authors.initials: T
authors.lastname: Yanagita
mesh_terms: D000818:Animals; D000982:Antipruritics; D005260:Female; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009019:Morphinans / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D012054:Reinforcement, Psychology; D012646:Self Administration; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000982:Antipruritics; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013141:Spiro Compounds; C111212:TRK 820
keywords: Monkey; Nalfurafine hydrochloride; Self-administration; TRK-820; κ opioid receptor