The histamine H4 receptor antagonist, JNJ 39758979, is effective in reducing histamine-induced pruritus in a randomized clinical study in healthy subjects

Journal of Pharmacology and Experimental Therapeutics

Volumn 350, Issue 1, 2014, Pages 181-187

  Kollmeier, Alexa ^a   Francke, Klaus ^b   Chen, Bin ^a   Dunford, Paul J ^a   Greenspan, Andrew J ^a   Xia, Yichuan ^a   Xu, Xie L ^a   Zhou, Bei ^a   Thurmond, Robin L ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b PAREXEL INTERNATIONAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (3 AMINOPYRROLIDIN 1 YL) 6 ISOPROPYLPYRIMIDIN 2 YLAMINE; CETIRIZINE; HISTAMINE; HISTAMINE H4 RECEPTOR ANTAGONIST; JNJ 39758979; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL STUDY; CONTROLLED STUDY; CROSSOVER PROCEDURE; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG WITHDRAWAL; HEADACHE; HUMAN; MALE; NAUSEA; PHARMACODYNAMICS; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; SINGLE DRUG DOSE; TOOTH INFECTION; URTICARIA;

ADOLESCENT; ADULT; CETIRIZINE; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; HEALTHY VOLUNTEERS; HISTAMINE; HISTAMINE ANTAGONISTS; HUMANS; MALE; MIDDLE AGED; PRURITUS; PYRIMIDINES; PYRROLIDINES; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, HISTAMINE; YOUNG ADULT;

EID: 84903517072     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.114.215749     Document Type: Article

References (35)

1. Bickford RG (1937) Experiments relating to the itch sensation, its peripheral mechanism, and central pathways. Clin Sci 3:377-386.
2. Coulie P, De Vos C, Ghys L, and Rihoux JP (1989) Pharmacologic modulation by cetirizine 2 hydrochloride and loratadine of the histamine-induced skin reaction in mice and in humans. Drug Dev Res 17:199-206. (Pubitemid 19190092)
3. Coulie PJ, Ghys L, and Rihoux JP (1991a) Histamine-induced wheal, flare, and pruritus: inhibition by cetirizine, terfenadine, and placebo. Drug Dev Res 23:269-274.
4. Coulie PJ, Ghys L, and Rihoux JP (1991b) Inhibitory effects of orally or sublingually administered cetirizine on histamine-induced weals and flares and their correlation with cetirizine plasma concentrations. J Int Med Res 19:174-179.
5. Cowden JM, Zhang M, Dunford PJ, and Thurmond RL (2010) The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol 130:1023-1033.
6. Dunford PJ, Williams KN, Desai PJ, Karlsson L, McQueen D, and Thurmond RL (2007) Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol 119:176-183. (Pubitemid 46037799)
7. Eppinger H (1913). über eine eigentümliche hautreaktion, hervorgerufen durch ergamin. Wien Med Wochenschr 23:1414.
8. Furue M, Terao H, and Koga T (2001) Effects of cetirizine and epinastine on the skin response to histamine iontophoresis. J Dermatol Sci 25:59-63. (Pubitemid 32012647)
9. Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, and Chatelain P (2002) Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194). Mol Pharmacol 61:391-399. (Pubitemid 34112814)
10. Grant JA, Danielson L, Rihoux J, and DeVos C (1999) A comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo in suppressing the cutaneous response to histamine. Int Arch Allergy Immunol 118:339-340. (Pubitemid 29195564)
11. Hosogi M, Schmelz M, Miyachi Y, and Ikoma A (2006) Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch. Pain 126:16-23. (Pubitemid 44751949)
12. Juhlin L, de Vos C, and Rihoux JP (1987) Inhibiting effect of cetirizine on histamineinduced and 48/80-induced wheals and flares, experimental dermographism, and cold-induced urticaria. J Allergy Clin Immunol 80:599-602. (Pubitemid 17164197)
13. Lahti A and Haapaniemi T (1993) Initiation of the effects of acrivastine and cetirizine on histamine-induced wheals and itch in human skin. Acta Derm Venereol 73:350-351. (Pubitemid 23310794)
14. Levander S, Ståhle-Bäckdahl M, and Hägermark O (1991) Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine. Eur J Clin Pharmacol 41:435-439.
15. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, and Leurs R (2005) Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 314:1310-1321. (Pubitemid 41205997)
16. Matsushita A, Seike M, Okawa H, Kadawaki Y, and Ohtsu H (2012) Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis. Exp Dermatol 21:714-715.
17. Morita E, Matsuo H, and Zhang Y (2005) Double-blind, crossover comparison of olopatadine and cetirizine versus placebo: suppressive effects on skin response to histamine iontophoresis. J Dermatol 32:58-61. (Pubitemid 40313066)
18. Ohsawa Y and Hirasawa N (2012) The antagonism of histamine H1 and H4 receptors ameliorates chronic allergic dermatitis via anti-pruritic and anti-inflammatory effects in NC/Nga mice. Allergy 67:1014-1022.
19. Rossbach K, Nassenstein C, Gschwandtner M, Schnell D, Sander K, Seifert R, Stark H, Kietzmann M, and Bäumer W (2011) Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience 190:89-102.
20. Rossbach K, Wendorff S, Sander K, Stark H, Gutzmer R, Werfel T, Kietzmann M, and Bäumer W (2009) Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp Dermatol 18:57-63.
21. Savall BM, Chavez F, Tays K, Dunford P, Cowden J, Hack MD, Wolin R, Thurmond RL, and Edwards JP (2014) Discovery and SAR of 6-alkyl-2,4- diaminopyrimidines as H4 receptor antagonists. J Med Chem 57: 2429-2439.
22. Schmelz M, Michael K, Weidner C, Schmidt R, Torebjörk HE, and Handwerker HO (2000) Which nerve fibers mediate the axon reflex flare in human skin? Neuroreport 11:645-648. (Pubitemid 30120491)
23. Schmelz M, Schmidt R, Bickel A, Handwerker HO, and Torebjörk HE (1997) Specific C-receptors for itch in human skin. J Neurosci 17:8003-8008. (Pubitemid 27426235)
24. Shin N, Covington M, Bian D, Zhuo J, Bowman K, Li Y, Soloviev M, Qian DQ, Feldman P, and Leffet L, et al. (2012) INCB38579, a novel and potent histamine H4 receptor small molecule antagonist with anti-inflammatory pain and anti-pruritic functions. Eur J Pharmacol 675:47-56.
25. Simone DA, Ngeow JYF, Whitehouse J, Becerra-Cabal L, Putterman GJ, and LaMotte RH (1987) The magnitude and duration of itch produced by intracutaneous injections of histamine. Somatosens Res 5:81-92. (Pubitemid 18090412)
26. Simons FE, McMillan JL, and Simons KJ (1990) A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects. J Allergy Clin Immunol 86:540-547. (Pubitemid 20372514)
27. Simons FE and Simons KJ (2011) Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 128:1139-1150, e4.
28. Sollmann T and Pilcher JD (1917) Endermic reactions. I. J Pharmacol 9:309-340.
29. Suwa E, Yamaura K, Oda M, Namiki T, and Ueno K (2011) Histamine H(4) receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model. Eur J Pharmacol 667:383-388.
30. Thurmond RL, Chen B, Dunford PJ, Greenspan AJ, Karlsson L, La D, Ward P, and Xu XL (2014a) Clinical and preclinical characterization of the histamine H(4) receptor antagonist JNJ-39758979. J Pharmacol Exp Ther 349:176-184.
31. Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung W-P, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, and Williams KN, et al. (2004) A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther 309:404-413. (Pubitemid 38393154)
32. Thurmond RL, Gelfand EW, and Dunford PJ (2008) The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 7:41-53.
33. Thurmond RL, Kazerouni K, Chaplan SR, and Greenspan AJ (2014b) Peripheral neuronal mechanism of itch 1. Histamine and itch, in Itch: Mechanisms and Treatment (Carstens EE and Akiyama T eds) pp 143-192, CRC Press, Boca Raton, FL.
34. Yamaura K, Oda M, Suwa E, Suzuki M, Sato H, and Ueno K (2009) Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist. J Toxicol Sci 34:427-431.
35. Yu F, Wolin RL, Wei J, Desai PJ, McGovern PM, Dunford PJ, Karlsson L, and Thurmond RL (2010) Pharmacological characterization of oxime agonists of the histamine H4 receptor. J. Recept Ligand Channel Res 3:37-49.