Uremic
pruritus has a great negative influence on quality of life in
hemodialysis (HD) patients and, importantly, negatively affects mortality risk. Recently,
nalfurafine hydrochloride, an
opioid κ-selective agonist, has been officially approved for resistant
pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. From clinical observation, it has been suggested that the upper neuron system plays a role in its pathogenesis. According to previous experimental results, using mice injected with
opioids,
dynorphin suppresses itch through binding κ-
opioid receptors, suggesting that κ-
opioid opioid receptor agonists act as potential therapeutic
reagents for
pruritus in HD patients. In Japan, a large-scale placebo-controlled study was performed to examine the efficacy and safety of oral
nalfurafine hydrochloride for intractable
pruritus in 337 HD patients. Two daily doses of 2.5 or 5 μg
nalfurafine or placebo were orally administered for 2 weeks, and clinical responses were analyzed. The results showed that the mean decrease in the visual analog scale for
pruritus from baseline was 22 mm in the 5 μg
nalfurafine hydrochloride group (n=114) and 23 mm in the 2.5 μg group (n=112). These reductions were statistically significant compared with 13 mm, which is the mean decrease of visual analog scale in the placebo group (n=111), demonstrating that
nalfurafine is an effective and safe
drug for uremic
pruritus in HD patients. Moreover, another open-label trial (n=145) examining the long-term effect of 5 μg oral
nalfurafine revealed the maintenance of the
antipruritic effect of
nalfurafine for 52 weeks. In addition, on the basis of recent data showing κ-
opioid receptor expression in the epidermis of
atopic dermatitis and
psoriasis,
nalfurafine hydrochloride also can be potentially used for these two
skin diseases.