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Crotamiton, an Anti-Scabies Agent, Suppresses Histamine- and Chloroquine-Induced Itch Pathways in Sensory Neurons and Alleviates Scratching in Mice  

Choi, Da-Som (College of Pharmacy, Gachon University)
Ji, Yeounjung (College of Pharmacy, Gachon University)
Jang, Yongwoo (Department of Biomedical Engineering, Hanyang University)
Lee, Wook-Joo (College of Pharmacy, Gachon University)
Shim, Won-Sik (College of Pharmacy, Gachon University)
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Biomolecules & Therapeutics / v.28, no.6, 2020 , pp. 569-575 More about this Journal
Crotamiton is an anti-scabies drug, but it was recently found that crotamiton also suppresses non-scabietic itching in mice. However, the underlying mechanism is largely unclear. Therefore, aim of the study is to investigate mechanisms of the anti-pruritic effect of crotamiton for non-scabietic itching. Histamine and chloroquine are used as non-scabietic pruritogens. The effect of crotamiton was identified using fluorometric intracellular calcium assays in HEK293T cells and primary cultured dorsal root ganglion (DRG) neurons. Further in vivo effect was evaluated by scratching behavior tests. Crotamiton strongly inhibited histamine-induced calcium influx in HEK293T cells, expressing both histamine receptor 1 (H1R) and transient receptor potential vanilloid 1 (TRPV1), as a model of histamine-induced itching. Similarly, it also blocked chloroquine-induced calcium influx in HEK293T cells, expressing both Mas-related G-protein-coupled receptor A3 (MRGPRA3) and transient receptor potential A1 (TRPA1), as a model of histamine-independent itching. Furthermore, crotamiton also suppressed both histamine- and chloroquine-induced calcium influx in primary cultures of mouse DRG. Additionally, crotamiton strongly suppressed histamine- and chloroquine-induced scratching in mice. Overall, it was found that crotamiton has an anti-pruritic effect against non-scabietic itching by histamine and chloroquine. Therefore, crotamiton may be used as a general anti-pruritic agent, irrespective of the presence of scabies.
Crotamiton; Itch; Histamine; Chloroquine; TRPV1; TRPA1;
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1 Akiyama, T., Ivanov, M., Nagamine, M., Davoodi, A., Carstens, M. I., Ikoma, A., Cevikbas, F., Kempkes, C., Buddenkotte, J., Steinhoff, M. and Carstens, E. (2016) Involvement of TRPV4 in serotoninevoked scratching. J. Invest. Dermatol. 136, 154-160.   DOI
2 Cho, Y., Jang, Y., Yang, Y. D., Lee, C. H., Lee, Y. and Oh, U. (2010) TRPM8 mediates cold and menthol allergies associated with mast cell activation. Cell Calcium 48, 202-208.   DOI
3 Couperus, M. (1949) The use of N-ethyl-o-crotonotoluidide in the treatment of scabies and various pruritic dermatoses. J. Invest. Dermatol. 13, 35-42.   DOI
4 Goldust, M., Rezaee, E. and Raghifar, R. (2014) Comparison of oral ivermectin versus crotamiton 10% cream in the treatment of scabies. Cutan. Ocul. Toxicol. 33, 333-336.   DOI
5 Guler, A. D., Lee, H., Iida, T., Shimizu, I., Tominaga, M. and Caterina, M. (2002) Heat-evoked activation of the ion channel, TRPV4. J. Neurosci. 22, 6408-6414.   DOI
6 Jang, Y., Jung, J., Kim, H., Oh, J., Jeon, J. H., Jung, S., Kim, K. T., Cho, H., Yang, D. J., Kim, S. M., Kim, I. B., Song, M. R. and Oh, U. (2012) Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth. J. Biol. Chem. 287, 6014-6024.   DOI
7 Jang, Y., Lee, W. J., Hong, G. S. and Shim, W. S. (2015) Red ginseng extract blocks histamine-dependent itch by inhibition of H1R/TRPV1 pathway in sensory neurons. J. Ginseng Res. 39, 257-264.   DOI
8 Larson, P. (2008) Review: topical permethrin was more effective than topical crotamiton or lindane for scabies. Evid. Based Nurs. 11, 47.   DOI
9 Kittaka, H. and Tominaga, M. (2017) The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin. Allergol. Int. 66, 22-30.   DOI
10 Kittaka, H., Yamanoi, Y. and Tominaga, M. (2017) Transient receptor potential vanilloid 4 (TRPV4) channel as a target of crotamiton and its bimodal effects. Pflugers Arch. 469, 1313-1323.   DOI
11 Lee, Y., Hong, S., Cui, M., Sharma, P. K., Lee, J. and Choi, S. (2015) Transient receptor potential vanilloid type 1 antagonists: a patent review (2011 - 2014). Expert Opin. Ther. Pat. 25, 291-318.   DOI
12 Malin, S. A., Davis, B. M. and Molliver, D. C. (2007) Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat. Protoc. 2, 152-160.   DOI
13 Schindelin, J., Rueden, C. T., Hiner, M. C. and Eliceiri, K. W. (2015) The ImageJ ecosystem: an open platform for biomedical image analysis. Mol. Reprod. Dev. 82, 518-529.   DOI
14 Ohsawa, Y. and Hirasawa, N. (2014) The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergol. Int. 63, 533-542.   DOI
15 Olatunde, A. and Obih, P. O. (1981) Use and misuse of 4-aminoquinoline antimalarials in tropical Africa and re-examination of itch reaction to these drugs. Trop. Doct. 11, 97-101.   DOI
16 Pradhananga, S. and Shim, W. S. (2015) Caffeic acid exhibits anti-pruritic effects by inhibition of multiple itch transmission pathways in mice. Eur. J. Pharmacol. 762, 313-321.   DOI
17 Vay, L., Gu, C. and McNaughton, P. A. (2012) The thermo-TRP ion channel family: properties and therapeutic implications. Br. J. Pharmacol. 165, 787-801.   DOI
18 Sekine, R., Satoh, T., Takaoka, A., Saeki, K. and Yokozeki, H. (2012) Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior. Exp. Dermatol. 21, 201-204.   DOI
19 Shim, W. S., Tak, M. H., Lee, M. H., Kim, M., Kim, M., Koo, J. Y., Lee, C. H., Kim, M. and Oh, U. (2007) TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J. Neurosci. 27, 2331-2337.   DOI
20 Smith, E. B., King, C. A. and Baker, M. D. (1984) Crotamiton lotion in pruritus. Int. J. Dermatol. 23, 684-685.   DOI
21 Wilson, S. R., Gerhold, K. A., Bifolck-Fisher, A., Liu, Q., Patel, K. N., Dong, X. and Bautista, D. M. (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat. Neurosci. 14, 595-602.   DOI
22 Veldhuis, N. A., Poole, D. P., Grace, M., McIntyre, P. and Bunnett, N. W. (2015) The G protein-coupled receptor-transient receptor potential channel axis: molecular insights for targeting disorders of sensation and inflammation. Pharmacol. Rev. 67, 36-73.   DOI
23 White, J. P., Urban, L. and Nagy, I. (2011) TRPV1 function in health and disease. Curr. Pharm. Biotechnol. 12, 130-144.   DOI