Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.

<h4>Background</h4>Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment wi...

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Autores principales:	Sonja Ständer, Dorothee Siepmann, Ilka Herrgott, Cord Sunderkötter, Thomas A Luger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa1def7bcaaf45d891b3ab7797963232
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spelling	oai:doaj.org-article:fa1def7bcaaf45d891b3ab77979632322021-12-02T20:21:10ZTargeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.1932-620310.1371/journal.pone.0010968https://doaj.org/article/fa1def7bcaaf45d891b3ab77979632322010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20532044/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.<h4>Methods and findings</h4>Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.<h4>Conclusions</h4>The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.Sonja StänderDorothee SiepmannIlka HerrgottCord SunderkötterThomas A LugerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e10968 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonja Ständer Dorothee Siepmann Ilka Herrgott Cord Sunderkötter Thomas A Luger Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
description	<h4>Background</h4>Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.<h4>Methods and findings</h4>Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.<h4>Conclusions</h4>The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.
format	article
author	Sonja Ständer Dorothee Siepmann Ilka Herrgott Cord Sunderkötter Thomas A Luger
author_facet	Sonja Ständer Dorothee Siepmann Ilka Herrgott Cord Sunderkötter Thomas A Luger
author_sort	Sonja Ständer
title	Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
title_short	Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
title_full	Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
title_fullStr	Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
title_full_unstemmed	Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
title_sort	targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fa1def7bcaaf45d891b3ab7797963232
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Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy.

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