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Topical non-peptide antagonists of sensory neurotransmitters substance P and CGRP do not modify patch test and prick test reactions: a vehicle-controlled, double-blind pilot study.

Wallengren, Joanna LU and Edvinsson, Lars LU (2014) In Archives for Dermatological Research 306(5). p.505-509
Abstract
Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim of this study was to examine the topical effects of non-peptide antagonists to substance P (aprepitant) and CGRP (telcagepant), respectively, on delayed and immediate reactions in the skin and on associated pruritus. A lipophilic formulation of aprepitant 5 % and a hydrophilic formulation of telcagepant 1 % were developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using... (More)
Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim of this study was to examine the topical effects of non-peptide antagonists to substance P (aprepitant) and CGRP (telcagepant), respectively, on delayed and immediate reactions in the skin and on associated pruritus. A lipophilic formulation of aprepitant 5 % and a hydrophilic formulation of telcagepant 1 % were developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL, suggesting there to be no impairment of the skin barrier. Permeation coefficients indicated moderate permeation. Histamine prick tests induced a flare with a mean area of 662 + 275 mm(2) and a weal with a mean volume of 49 + 11 mm(3). These reactions as well as histamine-induced pruritus were not affected significantly by any of the treatments. Treatment with aprepitant and its vehicle alone resulted in a potentiating of the infiltration of nickel reactions compared with test reactions obtained after no treatment (1147 + 423 mm(3) and 1427 + 566 mm(3) vs 683 +202 mm(3)) (p = 0.03). Telcagepant induced vasoconstriction in the skin but did not change the infiltration of nickel reactions. None of the treatments influenced the nickel patch test induced pruritus. The data suggest that the topical application of non-peptide antagonists penetrates the skin but does not inhibit contact dermatitis or pruritus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Archives for Dermatological Research
volume
306
issue
5
pages
505 - 509
publisher
Springer
external identifiers
  • pmid:24525842
  • wos:000338214900010
  • scopus:84903766520
ISSN
1432-069X
DOI
10.1007/s00403-014-1451-0
language
English
LU publication?
yes
id
b18baec9-0e7f-4439-acd8-520cd8fdf355 (old id 4334639)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24525842?dopt=Abstract
date added to LUP
2014-03-05 23:38:15
date last changed
2017-10-29 03:18:05
@article{b18baec9-0e7f-4439-acd8-520cd8fdf355,
  abstract     = {Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim of this study was to examine the topical effects of non-peptide antagonists to substance P (aprepitant) and CGRP (telcagepant), respectively, on delayed and immediate reactions in the skin and on associated pruritus. A lipophilic formulation of aprepitant 5 % and a hydrophilic formulation of telcagepant 1 % were developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL, suggesting there to be no impairment of the skin barrier. Permeation coefficients indicated moderate permeation. Histamine prick tests induced a flare with a mean area of 662 + 275 mm(2) and a weal with a mean volume of 49 + 11 mm(3). These reactions as well as histamine-induced pruritus were not affected significantly by any of the treatments. Treatment with aprepitant and its vehicle alone resulted in a potentiating of the infiltration of nickel reactions compared with test reactions obtained after no treatment (1147 + 423 mm(3) and 1427 + 566 mm(3) vs 683 +202 mm(3)) (p = 0.03). Telcagepant induced vasoconstriction in the skin but did not change the infiltration of nickel reactions. None of the treatments influenced the nickel patch test induced pruritus. The data suggest that the topical application of non-peptide antagonists penetrates the skin but does not inhibit contact dermatitis or pruritus.},
  author       = {Wallengren, Joanna and Edvinsson, Lars},
  issn         = {1432-069X},
  language     = {eng},
  number       = {5},
  pages        = {505--509},
  publisher    = {Springer},
  series       = {Archives for Dermatological Research},
  title        = {Topical non-peptide antagonists of sensory neurotransmitters substance P and CGRP do not modify patch test and prick test reactions: a vehicle-controlled, double-blind pilot study.},
  url          = {http://dx.doi.org/10.1007/s00403-014-1451-0},
  volume       = {306},
  year         = {2014},
}