Nalfurafine hydrochloride,a selective κ opioid receptor agonist,has no reinforcing effect on intravenous self-administration in rhesus monkeys

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. © 2015 japanese pharmacological society.