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
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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 mm2 and a weal with a mean volume of 49 + 11 mm3. 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 mm3 and 1427 + 566 mm3 vs 683 +202 mm3) (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.
KeywordsNeuropeptides Substance P Calcitonin Gene-Related Peptide Aprepitant Telcagepant Contact dermatitis
We are grateful to Assoc Prof Ola Bergendorff for performing calculation of the skin permeation coefficient. The study was supported by The Welander and Finsen Foundation and the Skane County Foundation.
Conflict of interest
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