| Theme |
New Drugs for Dialysis Patients |
| Title |
Novel κ-opioid receptor agonist (TRK-820) for pruritus in dialysis patients |
| Author |
Hiroo Kumagai |
Department of Kidney Disease and Hypertension, Keio University School of Medicine |
| Author |
Shiro Maruyama |
Department of Internal Medicine, Keinan General Hospital |
| Author |
Toshiya Ebata |
Chitofuna Dermatology Clinic |
| Author |
Hiromichi Suzuki |
Department of Kidney Disease, Saitama Medical School |
| Author |
Kenji Takamori |
Department of Dermatology, Urayasu Hospital, Juntendo University School of Medicine |
| [ Summary ] |
Itching may be induced by an imbalance between the μ and κ opioid systems in uremic pruritus patients. To examine the relationship between itch intensity and μ and κ opioid peptides, we determined serum concentrations of β-endorphin (endogenous μ agonist) and dynorphin-A (κ agonist). In hemodialysis patients with itch, the ratio of endogenous [β-endorphin / dynorphin-A] (the μ / κ ratio) increased in proportion to itch intensity, assessed by single regression analysis. On peripheral lymphocytes in healthy volunteer κ receptors were more dominantly expressed than μ receptors whereas μ receptors were dominant in patients, with itching determined by RT-PCR. Single oral doses of 10 μg of TRK-820 (a novel κ-receptor agonist) siginficantly reduced the visual analogue scale (VAS) of itching at 12 hours after oral administration in 6 patients. In a randomized prospective blind study enrolling 88 hemodialysis patients with severe itching, 14-day oral treatment with TRK-820 (5 μg / day) also significantly reduced the VAS compared with placebo. These data imply that the κ-receptor agonist TRK-820 is promising for the treatment of uremic pruritus. |