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.
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.
authors: Department of Clinical Sciences, Section of Dermatology, Lund University, Skane University Hospital, SE-221 85, Lund, Sweden, Joanna.Wallengren@med.lu.se.
authors: Joanna
authors: J
authors: Wallengren
authors: Lars
authors: L
authors: Edvinsson
mesh_terms: D000328:Adult; D000368:Aged; D000982:Antipruritics / Q000494:pharmacology / Q000627:therapeutic use; D000077608:Aprepitant; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors*; D003877:Dermatitis, Contact / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009532:Nickel / Q000009:adverse effects / Q000276:immunology; D010539:Permeability / Q000187:drug effects; D010865:Pilot Projects; D011537:Pruritus / Q000188:drug therapy*; D012867:Skin / Q000276:immunology; D012879:Skin Physiological Phenomena / Q000187:drug effects / Q000276:immunology; D012882:Skin Tests; D013373:Substance P / Q000037:antagonists & inhibitors*; D014581:Urticaria / Q000188:drug therapy; D014661:Vasoconstriction / Q000187:drug effects; D014870:Water Loss, Insensible / Q000187:drug effects; D055815:Young Adult
chemical_list: D000982:Antipruritics; D001381:Azepines; D007093:Imidazoles; D009025:Morpholines; D000077608:Aprepitant; D013373:Substance P; D009532:Nickel; C525458:telcagepant; D015740:Calcitonin Gene-Related Peptide