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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

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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 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.

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References

  1. Barber ED, Hill T, Schum DB (1995) The percutaneous absorption of hydroquinone (HQ) through rat and human skin in vitro. Toxicol Lett 80:167–172

    Article  CAS  PubMed  Google Scholar 

  2. Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J (2011) Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol 164:665–667

    CAS  PubMed  Google Scholar 

  3. Duval A, Dubertret L (2009) Aprepitant as an antipruritic agent? N Engl J Med 361:1415–1416

    Article  CAS  PubMed  Google Scholar 

  4. Edvinsson L, Linde (2010) M.New drugs in migraine treatment and prophylaxis: telcagepant and topiramate. Lancet 376:645–655

    Article  CAS  PubMed  Google Scholar 

  5. European Medicines Agency. Pharmaceutical quality system (ICH Q10) (2011) Available at: http://www.cdc.gov/niosh/topics/skin/skinPermCalc.html

  6. Frasch HF (2002) A random walk model of skin permeation. Risk Anal 22:265–276

    Article  PubMed  Google Scholar 

  7. Fregert S (1974) Patch testing. In: Fregert S (ed) Manual of contact dermatitis. Munksgaard, Copenhagen, p 53

    Google Scholar 

  8. Lodén M (1995) Biophysical properties of dry atopic and normal skin with special reference to effects of skin care products. Acta Derm Venereol Suppl 192:1–48

    Google Scholar 

  9. Potts RO, Guy RH (1992) Predicting skin permeability. Pharm Res 9:663–669

    Article  CAS  PubMed  Google Scholar 

  10. Reich A, Heisig M, Phan NQ, Taneda K, Takamori K, Takeuchi S, Furue M, Blome C, Augustin M, Ständer S, Szepietowski J (2012) Visual Analogue Scale: Evaluation of the Instrument for the Assessment of Pruritus. Acta Derm Venereol 92(5):497–501

    Article  PubMed  Google Scholar 

  11. Shah PP, Desai PR, Patel AR, Singh MS (2012) Skin permeating nanogel for the cutaneous co-delivery of two anti-inflammatory drugs. Biomaterials 33:1607–1617

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Shono Y, Jantratid E, Kesisoglou F, Reppas C, Dressman JB (2010) Forecasting in vivo oral absorption and food effect of micronized and nanosized aprepitant formulations in humans. Eur J Pharm Biopharm 76(1):95–104

    Article  CAS  PubMed  Google Scholar 

  13. Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA (2010) Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS ONE 5(6):e10968. doi:10.1371/journal.pone.0010968

    Article  PubMed Central  PubMed  Google Scholar 

  14. Wallengren J (1991) Substance P antagonist inhibits immediate and delayed type cutaneous hypersensitivity reactions. Br J Dermatol 124:324–328

    Article  CAS  PubMed  Google Scholar 

  15. Wallengren J (1999) Neuropeptides: Their significance in the skin. Drug News & Perspectives 12:401–411

    Article  CAS  Google Scholar 

  16. Wallengren J (2000) Dual effects of CGRP-antagonist on allergic contact dermatitis in human skin. Contact Dermatitis 43:137–143

    Article  CAS  PubMed  Google Scholar 

  17. Wallengren J (2012) Topical aprepitant does not attenuate clinical or experimental pruritus. Arch Dermatol 148(8):957–959

    Article  PubMed  Google Scholar 

  18. Wallengren J (2005) Neuroanatomy and neurophysiology of itch. Dermatol Ther 18(4):292–303

    Article  PubMed  Google Scholar 

  19. Wilschut A, ten Berge WF, Robinson PJ, McKone TE (1995) Estimating skin permeation. The validation of five mathematical skin permeation models. Chemosphere 30(7):1275–1296

    Article  CAS  PubMed  Google Scholar 

  20. Yosipovitch G, Duque MI, Patel TS, Ishiuji Y, Guzman-Sanchez DA, Dawn AG, Freedman BI, Chan YH, Crumrine D, Elias PM (2007) Skin barrier structure and function and their relationship to pruritus in end-stage renal disease. Nephrol Dial Transplant 22:3268–3279

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

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.

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Authors and Affiliations

  1. Department of Clinical Sciences, Section of Dermatology, Lund University, Skane University Hospital, SE-221 85, Lund, Sweden

    Joanna Wallengren

  2. Department of Clinical Sciences, Internal Medicine, Lund University, Skane University Hospital, SE-221 85, Lund, Sweden

    Lars Edvinsson

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  1. Joanna Wallengren
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  2. Lars Edvinsson
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Correspondence to Joanna Wallengren.

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Wallengren, J., Edvinsson, L. 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. Arch Dermatol Res 306, 505–509 (2014). https://doi.org/10.1007/s00403-014-1451-0

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  • DOI: https://doi.org/10.1007/s00403-014-1451-0

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