152658-17-8

Pruritus (chronic itching) is a common symptom seen in 25-90% of uremic patients, especially those with chronic renal failure requiring hemodialysis. Nalfurafine hydrochloride is a new member of this class that exhibits an improved safety profile as compared with its predecessors in preclinical studies. It is a potent agonist for the κ-opioid receptor (K_i = 0.24 nM, EC₅₀ = 0.008 nM, I_max = 91%), with substantially lower binding and agonism of the - or d-opioid receptors (K_i = 2.24 and 484 nM, EC₅₀ = 1.66 and 21.3 nM, I_max = 53 and 78%, respectively). In vivo, nalfurafine hydrochloride demonstrates potent antipruritic activity against histamine-sensitive as well as histamine-resistant itch in mouse pruritogen-induced scratching models.
The most common adverse event associated with nalfurafine hydrochloride was insomnia or sleep disturbance, seen in 10% of the treated patients. Nalfurafine is structurally related to naltrexone (Revia ), an opioid receptor antagonist marketed for treating alcohol dependence. Nalfurafine is synthesized in two steps starting from naltrexone, via reductive amination with methylamine under catalytic hydrogenation conditions, and subsequent acylation with 3(E)-(3-furyl) acryloyl chloride.

Toray industries (Japan)

Nalfurafine hydrochloride was launched on March of 2009 in Japan as the first in class non-narcotic opioid drug for intractable itch caused by hemodialysis. It showed significant opioid κ-agonist activity and induced neither aversion nor preference in rats on the CPP (Conditioned Place Preference) test. A new therapeutic agent for the treatment of uremic pruritus in hemodialysis patients.

Remitch