Nalfurafine

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Nalfurafine
Clinical data
Other namesTRK-820, AC-820, MT-9938
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Intravenous[1]
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life14 hours (acute);[2]
25–28 hours (chronic)[2]
Identifiers
  • (2E)-N-[(5α,6β)-17-(Cyclopropylmethyl)-3,14-dihydroxy-4,5-epoxymorphinan-6-yl]-3-(3-furyl)-N-methylacrylamide
JSmol)
  • CN([C@@H]1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O)C(=O)/C=C/C7=COC=C7
  • InChI=1S/C28H32N2O5/c1-29(23(32)7-4-18-9-13-34-16-18)20-8-10-28(33)22-14-19-5-6-21(31)25-24(19)27(28,26(20)35-25)11-12-30(22)15-17-2-3-17/h4-7,9,13,16-17,20,22,26,31,33H,2-3,8,10-12,14-15H2,1H3/b7-4+/t20-,22-,26+,27+,28-/m1/s1 ☒N
  • Key:XGZZHZMWIXFATA-UEZBDDGYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Nalfurafine (

INN, USAN)[3] (brand name Remitch; former developmental code names TRK-820, AC-820, MT-9938) is an antipruritic (anti-itch drug) that is marketed in Japan for the treatment of uremic pruritus in individuals with chronic kidney disease undergoing hemodialysis.[2][4] It activates the κ-opioid receptor (KOR)[5] and is potent, selective, and centrally active.[6] It was the first selective KOR agonist approved for clinical use.[7][8] It has also been dubiously referred to as the "first non-narcotic opioid drug" in history.[8]

History

Nalfurafine was derived from

animal models of nociception,[12] it was repurposed as an antipruritic at lower treatment doses due to an apparently unacceptable incidence of sedative effects in humans.[4][7] As of 2015, nalfurafine is also in clinical trials for the treatment of cholestatic pruritus in Japan for patients with chronic liver disease, and for the treatment of uremic pruritus in the United States.[4][13]

Effects

Unlike other KOR agonists, nalfurafine does not produce

antinociceptive, sedative, and diuretic effects.[6]

Mechanism of action

Nalfurafine is an orally active, centrally acting, highly potent, selective

β-arrestin signaling in vitro, but paradoxically, β-arrestin appears to be responsible for KOR agonist-induced aversion,[17] and nalfurafine furthermore shows paradoxical effects in vivo that are not consistent with its in vitro profile.[18]
As such, more research is needed to clarify the distinct mechanisms and effects of this drug.

Nalfurafine has been found in vitro to bind to the

affinity relative to the KOR.[19] However, in vivo, nalfurafine has shown no indications of MOR agonism or antagonism in animals or humans, including no evidence of rewarding or reinforcing effects or physical dependence.[19]

Research

Nalfurafine has been found to be effective in a variety of

addiction, and dependence, and may represent a novel potential treatment for these maladies.[6] In rodents, the drug attenuates the discriminative and rewarding effects of cocaine and the rewarding and locomotor effects of morphine, and diminishes the mecamylamine-precipitated aversive effect of nicotine withdrawal.[6]

See also

References

  1. ISBN 978-1-4939-2395-3
    .
  2. ^
    PMID 26005355
    .
  3. ^ Statement on a Nonproprietary Name adopted by the USAN Council
  4. ^
    ISBN 978-3-662-44605-8
    .
  5. PMID 36906681
    .
  6. ^
    ISBN 978-0-387-76678-2
    .
  7. ^
    ISBN 978-0-19-969739-7
    .
  8. ^
    ISBN 978-3-642-18107-8
    .
  9. ISBN 978-1-84973-645-9
    .
  10. PMID 19584962
    .
  11. ^ "Winfuran". European Medicines Agency - Human medicines. Archived from the original on 2016-08-19.
  12. PMID 10573186
    .
  13. ^ "Nalfurafine - Toray". AdisInsight. Springer Nature Switzerland AG.
  14. ^
    PMID 11325021
    .
  15. S2CID 25094224
    .
  16. ^
    PMID 9501472
    .
  17. PMID 26377476
    .
  18. ProQuest 1710058225
    .
  19. ^
    PMID 26786553
    .
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