More information on this family may be found on the IUPHAR-DB family and introduction pages.
Histamine receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Histamine Receptors, [10]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues (see [10]).
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Gemkow, MJ; Davenport, AJ; Harich, S; Ellenbroek, BA; Cesura, A; Hallett, D. (2009) The histamine H3 receptor as a therapeutic drug target for CNS disorders. Drug Discov. Today, 14 (9-10): 509-15. [PMID:19429511]
Haas, HL; Sergeeva, OA; Selbach, O. (2008) Histamine in the nervous system. Physiol. Rev., 88 (3): 1183-241. [PMID:18626069]
Hill, S. J., Ganellin, C. R., Timmerman, H., Schwartz, J. C., Shankley, N. P., Young, J. M., Schunack, W., Levi, R. and Haas, H. L. (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol. Rev., 49: 253-278. [PMID:9311023]
Leurs, R; Chazot, PL; Shenton, FC; Lim, HD; de Esch, IJ. (2009) Molecular and biochemical pharmacology of the histamine H4 receptor. Br. J. Pharmacol., 157 (1): 14-23. [PMID:19413568]
Panula, P; Nuutinen, S. (2011) Histamine and H3 receptor in alcohol-related behaviors. J. Pharmacol. Exp. Ther., 336 (1): 9-16. [PMID:20864504]
Passani, MB; Blandina, P; Torrealba, F. (2011) The histamine H3 receptor and eating behavior. J. Pharmacol. Exp. Ther., 336 (1): 24-9. [PMID:20864503]
Thurmond, RL; Gelfand, EW; Dunford, PJ. (2008) The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov, 7 (1): 41-53. [PMID:18172439]
Yanai, K; Tashiro, M. (2007) The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies. Pharmacol. Ther., 113 (1): 1-15. [PMID:16890992]
Zampeli, E; Tiligada, E. (2009) The role of histamine H4 receptor in immune and inflammatory disorders. Br. J. Pharmacol., 157 (1): 24-33. [PMID:19309354]
Zhang, M; Thurmond, RL; Dunford, PJ. (2007) The histamine H(4) receptor: a novel modulator of inflammatory and immune disorders. Pharmacol. Ther., 113 (3): 594-606. [PMID:17275092]
1. Beukers, M. W., Klaassen, C. H., De Grip, W. J., Verzijl, D., Timmerman, H. and Leurs, R. (1997) Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells. Br J Pharmacol, 122: 867-874. [PMID:9384502]
2. Booth, R. G., Moniri, N. H., Bakker, R. A., Choksi, N. Y., Nix, W. B., Timmerman, H. and Leurs, R. (2002) A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors. J Pharmacol Exp Ther, 302: 328-336. [PMID:12065734]
3. Chen, J., Liu, C. and Lovenberg, T. W. (2003) Molecular and pharmacological characterization of the mouse histamine H3 receptor. Eur J Pharmacol, 467: 57-65. [PMID:12706455]
4. Cogé, F., Guénin, S. P., Audinot, V., Renouard-Try, A., Beauverger, P., Macia, C., Ouvry, C., Nagel, N., Rique, H., Boutin, J. A. and Galizzi, J. P. (2001) Genomic organization and characterization of splice variants of the human histamine H3 receptor. Biochem J, 355: 279-288. [PMID:11284713]
5. De Backer, M. D., Loonen, I., Verhasselt, P., Neefs, J. M. and Luyten, W. H. (1998) Structure of the human histamine H1 receptor gene. Biochem J, 335: 663-670. [PMID:9794809]
6. Esbenshade, T. A., Fox, G. B., Krueger, K. M., Baranowski, J. L., Miller, T. R., Kang, C. H., Denny, L. I., Witte, D. G., Yao, B. B., Pan, J. B., Faghih, R., Bennani, Y. L., Williams, M. and Hancock, A. A. (2004) Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist. Biochem Pharmacol, 68: 933-945. [PMID:15294456]
7. Esbenshade, T. A., Krueger, K. M., Miller, T. R., Kang, C. H., Denny, L. I., Witte, D. G., Yao, B. B., Fox, G. B., Faghih, R., Bennani, Y. L., Williams, M. and Hancock, A. A. (2003) Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects. J Pharmacol Exp Ther, 305: 887-896. [PMID:12606603]
8. Gbahou, F., Vincent, L., Humbert-Claude, M., Tardivel-Lacombe, J., Chabret, C. and Arrang, J. M. (2006) Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives. Br J Pharmacol, 147: 744-754. [PMID:16432504]
9. Hancock, AA; Bennani, YL; Bush, EN; Esbenshade, TA; Faghih, R; Fox, GB; Jacobson, P; Knourek-Segel, V; Krueger, KM; Nuss, ME; et al.. (2004) Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist. Eur. J. Pharmacol., 487 (1-3): 183-97. [PMID:15033391]
10. Hill, S. J., Ganellin, C. R., Timmerman, H., Schwartz, J. C., Shankley, N. P., Young, J. M., Schunack, W., Levi, R. and Haas, H. L. (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol. Rev., 49: 253-278. [PMID:9311023]
11. Ishiwata, K; Kawamura, K; Wang, WF; Tsukada, H; Harada, N; Mochizuki, H; Kimura, Y; Ishii, K; Iwata, R; Yanai, K. (2004) Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species. Nucl. Med. Biol., 31 (4): 493-502. [PMID:15093820]
12. Jansen, FP; Wu, TS; Voss, HP; Steinbusch, HW; Vollinga, RC; Rademaker, B; Bast, A; Timmerman, H. (1994) Characterization of the binding of the first selective radiolabelled histamine H3-receptor antagonist, [125I]-iodophenpropit, to rat brain. Br. J. Pharmacol., 113 (2): 355-62. [PMID:7834183]
13. Kitbunnadaj, R., Hashimoto, T., Poli, E., Zuiderveld, O. P., Menozzi, A., Hidaka, R., de Esch, I. J., Bakker, R. A., Menge, W. M., Yamatodani, A., Coruzzi, G., Timmerman, H. and Leurs, R. (2005) N-substituted piperidinyl alkyl imidazoles: discovery of methimepip as a potent and selective histamine H3 receptor agonist. J Med Chem, 48: 2100-2107. [PMID:15771452]
14. Kitbunnadaj, R; Zuiderveld, OP; Christophe, B; Hulscher, S; Menge, WM; Gelens, E; Snip, E; Bakker, RA; Celanire, S; Gillard, M; et al.. (2004) Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist. J. Med. Chem., 47 (10): 2414-7. [PMID:15115383]
15. Kraus, A; Ghorai, P; Birnkammer, T; Schnell, D; Elz, S; Seifert, R; Dove, S; Bernhardt, G; Buschauer, A. (2009) N(G)-acylated aminothiazolylpropylguanidines as potent and selective histamine H(2) receptor agonists. ChemMedChem, 4 (2): 232-40. [PMID:19072936]
16. Kühn, B., Schmid, A., Harteneck, C., Gudermann, T. and Schultz, G. (1996) G proteins of the Gq family couple the H2 histamine receptor to phospholipase C. Mol Endocrinol, 10: 1697-1707. [PMID:8961278]
17. Leurs, R; Smit, MJ; Menge, WM; Timmerman, H. (1994) Pharmacological characterization of the human histamine H2 receptor stably expressed in Chinese hamster ovary cells. Br. J. Pharmacol., 112 (3): 847-54. [PMID:7921611]
18. Ligneau, X., Morisset, S., Tardivel-Lacombe, J., Gbahou, F., Ganellin, C. R., Stark, H., Schunack, W., Schwartz, J. C. and Arrang, J. M. (2000) Distinct pharmacology of rat and human histamine H(3) receptors: role of two amino acids in the third transmembrane domain. Br J Pharmacol, 131: 1247-1250. [PMID:11090094]
19. Lim, H. D., Smits, R. A., Bakker, R. A., van Dam, C. M., de Esch, I. J. and Leurs, R. (2006) Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist. J Med Chem, 49: 6650-6651. [PMID:17154494]
20. Lim, H. D., van Rijn, R. M., Ling, P., Bakker, R. A., Thurmond, R. L. 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. [PMID:15947036]
21. Liu, C., Ma, X., Jiang, X., Wilson, S. J., Hofstra, C. L., Blevitt, J., Pyati, J., Li, X., Chai, W., Carruthers, N. and Lovenberg, T. W. (2001) Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol, 59: 420-426. [PMID:11179434]
22. Liu, C., Wilson, S. J., Kuei, C. and Lovenberg, T. W. (2001) Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther, 299: 121-130. [PMID:11561071]
23. Lovenberg, T. W., Pyati, J., Chang, H., Wilson, S. J. and Erlander, M. G. (2000) Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. J Pharmacol Exp Ther, 293: 771-778. [PMID:10869375]
24. Moguilevsky, N., Varsalona, F., Noyer, M., Gillard, M., Guillaume, J. P., Garcia, L., Szpirer, C., Szpirer, J. and Bollen, A. (1994) Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene. Eur J Biochem, 224: 489-495. [PMID:7925364]
25. Monczor, F; Fernandez, N; Legnazzi, BL; Riveiro, ME; Baldi, A; Shayo, C; Davio, C. (2003) Tiotidine, a histamine H2 receptor inverse agonist that binds with high affinity to an inactive G-protein-coupled form of the receptor. Experimental support for the cubic ternary complex model. Mol. Pharmacol., 64 (2): 512-20. [PMID:12869657]
26. Morse, K. L., Behan, J., Laz, T. M., West, R. E., Greenfeder, S. A., Anthes, J. C., Umland, S., Wan, Y., Hipkin, R. W., Gonsiorek, W., Shin, N., Gustafson, E. L., Qiao, X., Wang, S., Hedrick, J. A., Greene, J., Bayne, M. and Monsma, F. J. (2001) Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther, 296: 1058-1066. [PMID:11181941]
27. Nakamura, T., Itadani, H., Hidaka, Y., Ohta, M. and Tanaka, K. (2000) Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Commun, 279: 615-620. [PMID:11118334]
28. Nguyen, T., Shapiro, D. A., George, S. R., Setola, V., Lee, D. K., Cheng, R., Rauser, L., Lee, S. P., Lynch, K. R., Roth, B. L. and O'Dowd, B. F. (2001) Discovery of a novel member of the histamine receptor family. Mol Pharmacol, 59: 427-433. [PMID:11179435]
29. Oda, T., Morikawa, N., Saito, Y., Masuho, Y. and Matsumoto, S. (2000) Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem, 275: 36781-36786. [PMID:10973974]
30. Ratnala, V. R., Swarts, H. G., VanOostrum, J., Leurs, R., DeGroot, H. J., Bakker, R. A. and DeGrip, W. J. (2004) Large-scale overproduction, functional purification and ligand affinities of the His-tagged human histamine H1 receptor. Eur J Biochem, 271: 2636-2646. [PMID:15206929]
31. Schotte, A., Janssen, P. F., Gommeren, W., Luyten, W. H., Van Gompel, P., Lesage, A. S., De Loore, K. and Leysen, J. E. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl), 124: 57-73. [PMID:8935801]
32. Seifert, R., Wenzel-Seifert, K., Burckstummer, T., Pertz, H. H., Schunack, W., Dove, S., Buschauer, A. and Elz, S. (2003) Multiple differences in agonist and antagonist pharmacology between human and guinea pig histamine H1-receptor. J Pharmacol Exp Ther, 305: 1104-1115. [PMID:12626648]
33. Smits, RA; Lim, HD; Stegink, B; Bakker, RA; de Esch, IJ; Leurs, R. (2006) Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. J. Med. Chem., 49 (15): 4512-6. [PMID:16854056]
34. Thurmond, R. L., Desai, P. J., Dunford, P. J., Fung-Leung, W. P., Hofstra, C. L., Jiang, W., Nguyen, S., Riley, J. P., Sun, S., Williams, K. N., Edwards, J. P. and Karlsson, L. (2004) A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther, 309: 404-413. [PMID:14722321]
35. Wieland, K., Bongers, G., Yamamoto, Y., Hashimoto, T., Yamatodani, A., Menge, W. M., Timmerman, H., Lovenberg, T. W. and Leurs, R. (2001) Constitutive activity of histamine h(3) receptors stably expressed in SK-N-MC cells: display of agonism and inverse agonism by H(3) antagonists. J Pharmacol Exp Ther, 299: 908-914. [PMID:11714875]
36. Wulff, B. S., Hastrup, S. and Rimvall, K. (2002) Characteristics of recombinantly expressed rat and human histamine H3 receptors. Eur J Pharmacol, 453: 33-41. [PMID:12393057]
37. Zhu, Y., Michalovich, D., Wu, H., Tan, K. B., Dytko, G. M., Mannan, I. J., Boyce, R., Alston, J., Tierney, L. A., Li, X., Herrity, N. C., Vawter, L., Sarau, H. M., Ames, R. S., Davenport, C. M., Hieble, J. P., Wilson, S., Bergsma, D. J. and Fitzgerald, L. R. (2001) Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Mol Pharmacol, 59: 434-441. [PMID:11179436]
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histaprodifen and methylhistaprodifen are reduced efficacy agonists. The H4 receptor appears to exhibit broadly similar pharmacology to the H3 receptor for imidazole-containing ligands, although (R)-α-methylhistamine and N-α-methylhistamine are less potent, while clobenpropit acts as a reduced efficacy agonist [21,27-29,37]. Moreover, 4-methylhistamine is identified as a high affinity, full agonist for the human H4 receptor [20]. [3H]histamine has been used to label the H4 receptor in heterologous expression systems.