Article ; Online: Antipruritic Effect of Nalbuphine, a Kappa Opioid Receptor Agonist, in Mice: A Pan Antipruritic.
Molecules (Basel, Switzerland)
2021 Volume 26, Issue 18
Abstract: Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models ... nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases ... chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine ...
| Abstract | Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models of acute and chronic scratching (itchlike behavior). Three KOR agonists, nalfurafine, difelikefalin, and nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases. Nalfurafine (in Japan) and difelikefalin (in the USA) were approved to be used in the treatment of chronic itch in hemodialysis patients. The FDA-approved nalbuphine has been used in clinic for over 40 years, and it is the only narcotic agonist that is not scheduled. We aimed to study (a) antiscratch activity of nalbuphine against TAT-HIV-1 protein (controls HIV transcription)-, deoxycholic acid (DCA, bile acid)-, and chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine is produced via KORs. First, dose-responses were developed for pruritogens. Mice were pretreated with nalbuphine (0.3-10 mg/kg) and then a submaximal dose of pruritogens were administered and the number of scratching bouts was counted. To study if the antiscratch effect of nalbuphine is produced via KOR, we used KOR knock out mice and pharmacologic inhibition of KORs using nor-binaltorphimine, a KOR antagonist. For this aim, we used CQ as a pruritogen. We found that: (a) TAT-HIV-1 protein elicits scratching in a dose-dependent manner; (b) nalbuphine inhibits scratching induced by TAT-HIV-1, DCA, and CQ dose-dependently; and (c) nalbuphine inhibits scratching induced by CQ through KORs. In conclusion, nalbuphine inhibits scratching elicited by multiple pruritogens. |
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| MeSH term(s) | Animals ; Antipruritics/pharmacology ; Antipruritics/therapeutic use ; Behavior, Animal/drug effects ; Chloroquine/toxicity ; Deoxycholic Acid/toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Male ; Mice ; Nalbuphine/pharmacology ; Nalbuphine/therapeutic use ; Naltrexone/analogs & derivatives ; Naltrexone/pharmacology ; Naltrexone/therapeutic use ; Narcotic Antagonists/pharmacology ; Narcotic Antagonists/therapeutic use ; Pruritus/chemically induced ; Pruritus/prevention & control ; Receptors, Opioid, kappa/agonists ; Receptors, Opioid, kappa/antagonists & inhibitors ; Receptors, Opioid, kappa/genetics ; Receptors, Opioid, kappa/metabolism ; tat Gene Products, Human Immunodeficiency Virus/toxicity |
| Chemical Substances | Antipruritics ; Narcotic Antagonists ; Receptors, Opioid, kappa ; tat Gene Products, Human Immunodeficiency Virus ; Deoxycholic Acid (005990WHZZ) ; norbinaltorphimine (36OOQ86QM1) ; Naltrexone (5S6W795CQM) ; Chloroquine (886U3H6UFF) ; Nalbuphine (L2T84IQI2K) |
| Language | English |
| Publishing date | 2021-09-11 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 1413402-0 |
| ISSN | 1420-3049 ; 1431-5165 ; 1420-3049 |
| ISSN (online) | 1420-3049 |
| ISSN | 1431-5165 ; 1420-3049 |
| DOI | 10.3390/molecules26185517 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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