Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [18,41]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [18]. The human and rat H₃ receptor genes are subject to significant splice variance [3]. The potency order of histamine at histamine receptor subtypes is H₃ = H₄ > H₂ > H₁ [41]. Some agonists at the human H₃ receptor display significant ligand bias [46]. Antagonists of all 4 histamine receptors have clinical uses: H₁ antagonists for allergies (e.g. cetirizine), H₂ antagonists for acid-reflux diseases (e.g. ranitidine), H₃ antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H₄ antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [41] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [1,52].
Histamine receptor photopharmacology has provided both agonist and antagonist tools to achieve optical control over H₃ receptor function. The best-characterized agonist is VUF15000, an azobenzene-containing compound in which the trans-isomer binds the H₃ receptor with nanomolar affinity (K_i = 4 nM) and behaves as a full agonist. Its cis-isomer is approximately 10-fold less active, thereby creating a reversible light-controlled switch for receptor activation that has been validated in binding, NanoBRET biosensor, and electrophysiology assays [17]. Also several photoswitchable antagonists have been established as tools for histamine H₃ receptor photopharmacology. The first-generation azobenzene-based antagonists included VUF14738 and VUF14862, which are part of a bidirectional toolbox [16]. VUF14738 (trans: K_i = 631 nM) shows a light-induced 10-fold increase in affinity, while VUF14862 (trans: K_i = 1.6 nM) displays the opposite, with more than a tenfold change upon illumination. Both compounds are highly fatigue-resistant, underwent rapid trans-cis isomerization, and had long thermal half-lives, allowing reversible optical control in binding and electrophysiological assays. Building on these scaffolds, recently 2nd generation ligands were developed to overcome limitations of azobenzenes [5]. The arylazopyrazole-based antagonist VUF26063 displayed subnanomolar affinity at the H₃ receptor in its trans isomer (K_i = 0.5 nM) and a 50-fold lower affinity in the cis state. This compound showed robust switching with high photostationary state efficiency and improved aqueous solubility compared to earlier analogues. Importantly, radiolabeling yielded [³H]VUF26063, the first radiolabeled photoswitchable GPCR ligand, enabling the direct study of ligand binding kinetics and photoisomerization inside the receptor pocket in real time. These antagonists, together with the agonist VUF15000, provide a well-characterized toolkit of photosensitive ligands that can be used to dissect H₃ receptor pharmacology with spatiotemporal precision.

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 at the H₄ receptor and an antagonist at the H₃ receptor [30,38-40,55]. Moreover, 4-methylhistamine is identified as a high affinity, full agonist for the human H₄ receptor [29]. [³H]Histamine has been used to label the H₄ receptor in heterologous expression systems.

* Key recommended reading is highlighted with an asterisk

Berlin M, Boyce CW, Ruiz Mde L. (2011) Histamine H3 receptor as a drug discovery target. J Med Chem, 54 (1): 26-53. [PMID:21062081]

* Gbahou F, Rouleau A, Arrang JM. (2012) The histamine autoreceptor is a short isoform of the H₃ receptor. Br J Pharmacol, 166 (6): 1860-71. [PMID:22356432]

Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL. (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev, 49 (3): 253-78. [PMID:9311023]

Leurs R, Vischer HF, Wijtmans M, de Esch IJ. (2011) En route to new blockbuster anti-histamines: surveying the offspring of the expanding histamine receptor family. Trends Pharmacol Sci, 32 (4): 250-7. [PMID:21414671]

* Nieto-Alamilla G, Márquez-Gómez R, García-Gálvez AM, Morales-Figueroa GE, Arias-Montaño JA. (2016) The Histamine H3 Receptor: Structure, Pharmacology, and Function. Mol Pharmacol, 90 (5): 649-673. [PMID:27563055]

* Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015) International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors. Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]

Passani MB, Blandina P. (2011) Histamine receptors in the CNS as targets for therapeutic intervention. Trends Pharmacol Sci, 32 (4): 242-9. [PMID:21324537]

Schwartz JC. (2011) The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol, 163 (4): 713-21. [PMID:21615387]

* van Rijn RM, van Marle A, Chazot PL, Langemeijer E, Qin Y, Shenton FC, Lim HD, Zuiderveld OP, Sansuk K, Dy M et al.. (2008) Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor. Biochem J, 414 (1): 121-31. [PMID:18452403]

1. Attali P, Gomeni R, Wersinger E, Poli S, Venail F. (2016) The Effects of SENS-111, A New H4R Antagonist, On Vertigo Induced by Caloric Test in Healthy Volunteers (HV) is Related to Plasma Concentrations. Clin Ther, 38 (10S): e4. [PMID:27673668]

2. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

3. Bakker RA, Lozada AF, van Marle A, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM et al.. (2006) Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant-negative isoforms. Mol Pharmacol, 69 (4): 1194-206. [PMID:16415177]

4. Beukers MW, Klaassen CH, De Grip WJ, Verzijl D, Timmerman H, Leurs R. (1997) Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells. Br J Pharmacol, 122 (5): 867-74. [PMID:9384502]

5. Binkhorst LCP, Josimovic I, De Boer B, Simon IA, Van Der Aa F, Zarzycka BA, De Esch IJP, Vischer HF, Windhorst AD, Wijtmans M et al.. (2025) A Radiolabeled Photoswitchable G Protein-Coupled Receptor Antagonist Enlightens Ligand Binding Kinetics Associated with Photoswitching. J Am Chem Soc, 147 (27): 23991-24000. [PMID:40568883]

6. Booth RG, Moniri NH, Bakker RA, Choksi NY, Nix WB, Timmerman H, Leurs R. (2002) A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors. J Pharmacol Exp Ther, 302 (1): 328-36. [PMID:12065734]

7. Cappelli A, Manini M, Valenti S, Castriconi F, Giuliani G, Anzini M, Brogi S, Butini S, Gemma S, Campiani G et al.. (2013) Synthesis and structure-activity relationship studies in serotonin 5-HT1A receptor agonists based on fused pyrrolidone scaffolds. Eur J Med Chem, 63: 85-94. [PMID:23466604]

8. Chen J, Liu C, Lovenberg TW. (2003) Molecular and pharmacological characterization of the mouse histamine H3 receptor. Eur J Pharmacol, 467 (1-3): 57-65. [PMID:12706455]

9. Cogé F, Guénin SP, Audinot V, Renouard-Try A, Beauverger P, Macia C, Ouvry C, Nagel N, Rique H, Boutin JA et al.. (2001) Genomic organization and characterization of splice variants of the human histamine H3 receptor. Biochem J, 355 (Pt 2): 279-88. [PMID:11284713]

10. De Backer MD, Loonen I, Verhasselt P, Neefs JM, Luyten WH. (1998) Structure of the human histamine H1 receptor gene. Biochem J, 335 ( Pt 3): 663-70. [PMID:9794809]

11. Esbenshade TA, Fox GB, Krueger KM, Baranowski JL, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan JB et al.. (2004) Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist. Biochem Pharmacol, 68 (5): 933-45. [PMID:15294456]

12. Esbenshade TA, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Fox GB, Faghih R, Bennani YL et al.. (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 (3): 887-96. [PMID:12606603]

13. Gbahou F, Vincent L, Humbert-Claude M, Tardivel-Lacombe J, Chabret C, Arrang JM. (2006) Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives. Br J Pharmacol, 147 (7): 744-54. [PMID:16432504]

14. Ghoneim OM, Legere JA, Golbraikh A, Tropsha A, Booth RG. (2006) Novel ligands for the human histamine H1 receptor: synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes. Bioorg Med Chem, 14 (19): 6640-58. [PMID:16782354]

15. 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]

16. Hauwert NJ, Mocking TAM, Da Costa Pereira D, Kooistra AJ, Wijnen LM, Vreeker GCM, Verweij EWE, De Boer AH, Smit MJ, De Graaf C et al.. (2018) Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. J Am Chem Soc, 140 (12): 4232-4243. [PMID:29470065]

17. Hauwert NJ, Mocking TAM, Da Costa Pereira D, Lion K, Huppelschoten Y, Vischer HF, De Esch IJP, Wijtmans M, Leurs R. (2019) A Photoswitchable Agonist for the Histamine H₃ Receptor, a Prototypic Family A G-Protein-Coupled Receptor. Angew Chem Int Ed Engl, 58 (14): 4531-4535. [PMID:30735597]

18. Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL. (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev, 49 (3): 253-78. [PMID:9311023]

19. 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]

20. 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]

21. Kitbunnadaj R, Hashimoto T, Poli E, Zuiderveld OP, Menozzi A, Hidaka R, de Esch IJ, Bakker RA, Menge WM, Yamatodani A et al.. (2005) N-substituted piperidinyl alkyl imidazoles: discovery of methimepip as a potent and selective histamine H3 receptor agonist. J Med Chem, 48 (6): 2100-7. [PMID:15771452]

22. 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]

23. 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]

24. Kühn B, Schmid A, Harteneck C, Gudermann T, Schultz G. (1996) G proteins of the Gq family couple the H2 histamine receptor to phospholipase C. Mol Endocrinol, 10: 1697-1707. [PMID:8961278]

25. 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]

26. Lewis TA, Young MA, Arrington MP, Bayless L, Cai X, Collart P, Eckman JB, Ellis JL, Ene DG, Libertine L et al.. (2004) Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett, 14 (22): 5591-4. [PMID:15482930]

27. Ligneau X, Morisset S, Tardivel-Lacombe J, Gbahou F, Ganellin CR, Stark H, Schunack W, Schwartz JC, Arrang JM. (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 (7): 1247-50. [PMID:11090094]

28. Lim HD, Smits RA, Bakker RA, van Dam CM, de Esch IJ, Leurs R. (2006) Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist. J Med Chem, 49 (23): 6650-1. [PMID:17154494]

29. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, 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 (3): 1310-21. [PMID:15947036]

30. Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, Pyati J, Li X, Chai W, Carruthers N et al.. (2001) Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol, 59 (3): 420-6. [PMID:11179434]

31. Liu C, Wilson SJ, Kuei C, Lovenberg TW. (2001) Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther, 299 (1): 121-30. [PMID:11561071]

32. Lovenberg TW, Pyati J, Chang H, Wilson SJ, Erlander MG. (2000) Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. J Pharmacol Exp Ther, 293 (3): 771-8. [PMID:10869375]

33. Medhurst AD, Atkins AR, Beresford IJ, Brackenborough K, Briggs MA, Calver AR, Cilia J, Cluderay JE, Crook B, Davis JB et al.. (2007) GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther, 321 (3): 1032-45. [PMID:17327487]

34. Moguilevsky N, Varsalona F, Noyer M, Gillard M, Guillaume JP, Garcia L, Szpirer C, Szpirer J, 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 (2): 489-95. [PMID:7925364]

35. 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]

36. Morse KL, Behan J, Laz TM, West Jr RE, Greenfeder SA, Anthes JC, Umland S, Wan Y, Hipkin RW, Gonsiorek W et al.. (2001) Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther, 296 (3): 1058-66. [PMID:11181941]

37. Nagase T, Mizutani T, Ishikawa S, Sekino E, Sasaki T, Fujimura T, Ito S, Mitobe Y, Miyamoto Y, Yoshimoto R et al.. (2008) Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem, 51 (15): 4780-9. [PMID:18598020]

38. Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K. (2000) Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Commun, 279 (2): 615-20. [PMID:11118334]

39. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL et al.. (2001) Discovery of a novel member of the histamine receptor family. Mol Pharmacol, 59 (3): 427-33. [PMID:11179435]

40. Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S. (2000) Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem, 275 (47): 36781-6. [PMID:10973974]

41. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015) International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors. Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]

42. Pearlstein R, Vaz R, Rampe D. (2003) Understanding the structure-activity relationship of the human ether-a-go-go-related gene cardiac K+ channel. A model for bad behavior. J Med Chem, 46 (11): 2017-22. [PMID:12747773]

43. Petremann M, Gueguen C, Delgado Betancourt V, Wersinger E, Dyhrfjeld-Johnsen J. (2020) Effect of the novel histamine H₄ receptor antagonist SENS-111 on spontaneous nystagmus in a rat model of acute unilateral vestibular loss. Br J Pharmacol, 177 (3): 623-633. [PMID:31347148]

44. Procopiou PA, Browning C, Buckley JM, Clark KL, Fechner L, Gore PM, Hancock AP, Hodgson ST, Holmes DS, Kranz M et al.. (2011) The discovery of phthalazinone-based human H1 and H3 single-ligand antagonists suitable for intranasal administration for the treatment of allergic rhinitis. J Med Chem, 54 (7): 2183-95. [PMID:21381763]

45. Ratnala VR, Swarts HG, VanOostrum J, Leurs R, DeGroot HJ, Bakker RA, DeGrip WJ. (2004) Large-scale overproduction, functional purification and ligand affinities of the His-tagged human histamine H1 receptor. Eur J Biochem, 271 (13): 2636-46. [PMID:15206929]

46. Riddy DM, Cook AE, Diepenhorst NA, Bosnyak S, Brady R, Mannoury la Cour C, Mocaer E, Summers RJ, Charman WN, Sexton PM et al.. (2017) Isoform-Specific Biased Agonism of Histamine H3 Receptor Agonists. Mol Pharmacol, 91 (2): 87-99. [PMID:27864425]

47. Savall BM, Chavez F, Tays K, Dunford PJ, Cowden JM, Hack MD, Wolin RL, Thurmond RL, Edwards JP. (2014) Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H₄ receptor antagonists. J Med Chem, 57 (6): 2429-39. [PMID:24495018]

48. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl.), 124 (1-2): 57-73. [PMID:8935801]

49. Seifert R, Wenzel-Seifert K, Burckstummer T, Pertz HH, Schunack W, Dove S, Buschauer A, Elz S. (2003) Multiple differences in agonist and antagonist pharmacology between human and guinea pig histamine H1-receptor. J Pharmacol Exp Ther, 305 (3): 1104-15. [PMID:12626648]

50. 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]

51. Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, Nguyen S, Riley JP, Sun S, Williams KN, Edwards JP, Karlsson L. (2004) A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther, 309: 404-413. [PMID:14722321]

52. Venail F, Attali P, Wersinger E, Gomeni R, Poli S, Schmerber S. (2018) Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H₄ receptor inhibitor SENS-111 using a modified caloric test in healthy subjects. Br J Clin Pharmacol, 84 (12): 2836-2848. [PMID:30152527]

53. Wieland K, Bongers G, Yamamoto Y, Hashimoto T, Yamatodani A, Menge WM, Timmerman H, Lovenberg TW, 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 (3): 908-14. [PMID:11714875]

54. Wulff BS, Hastrup S, Rimvall K. (2002) Characteristics of recombinantly expressed rat and human histamine H3 receptors. Eur J Pharmacol, 453 (1): 33-41. [PMID:12393057]

55. Zhu Y, Michalovich D, Wu H, Tan KB, Dytko GM, Mannan IJ, Boyce R, Alston J, Tierney LA, Li X et al.. (2001) Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Mol Pharmacol, 59 (3): 434-41. [PMID:11179436]

56. Łazewska D, Kuder K, Ligneau X, Camelin JC, Schunack W, Stark H, Kieć-Kononowicz K. (2009) Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands. Bioorg Med Chem, 17 (8): 3037-42. [PMID:19329325]

Subcommittee members: Paul Chazot (Co-chairperson) School of Biological and Biomedical Sciences Durham University South Road Durham DH1 3LE UK Rob Leurs (Co-chairperson) Leiden/Amsterdam Center for Drug Research (LACDR) Division of Medicinal Chemistry Faculty of Science VU University Amsterdam De Boelelaan 1083 1081 HV Amsterdam The Netherlands Marlon Cowart Dept. Neuroscience Research Abbott Laboratories AP9a/216, GPRD_R4MN 100 Abbott Park Road IL 60064-6123 Abbott Park USA Ralf Gutzmer Hannover Medical School Dept. of Dermatology 30449 Hannover Germany Helmut L. Haas Department of Physiology Heinrich Heine University Dusseldorf W-40001 Germany Steve Liu Pfizer Global Research & Development Kent UK Pertti Panula Biomedicum Helsinki P.O. Box 63 FIN-00014 University of Helsinki Jean-Charles Schwartz Unité de Neurobiologie et Pharmacologie Moléculaire INSERM U109 Centre Paul Broca 2ter rue d'Alésia Paris 75014 France Roland Seifert Institute of Pharmacology Medical School of Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Holger Stark Goethe University Institute of Pharmaceutical Chemistry ZAFES/CMP/ICNP Max-von-Laue Str. 9 60438 Frankfurt/Main Germany Robin Thurmond Johnson & Johnson Pharmaceutical Research & Development 3210 Merryfield Row San Diego CA 92121 USA

Other contributors: Hiroyuki Fukui Department of Pharmacology The University of Tokushima Faculty of Pharmaceutical Sciences Tokushima 770-0044 Japan C. Robin Ganellin Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street London WC1H 0AJ UK Stephen J. Hill (Past chairperson) Institute of Cell Signalling Medical School Queen's Medical Centre Nottingham NG7 2UH UK Rebecca Hills (Past curator) Roberto Levi Department of Pharmacology Cornell University Medical College 1300 York Avenue New York NY 10021 USA Walter Schunack Institut fur Pharmazie Freie Universitat Berlin Konigin-Luise-Strasse 2 and 4 Berlin D-14195 Germany Nigel P. Shankley R. W. Johnson Pharmaceutical Research Institute 3210 Merryfield Row San Diego CA 92121 USA Henk Timmerman Department of Pharmacology Leiden-Amsterdam Center for Drug Research Vrije Universiteit De Boelelaan 1083 Amsterdam 1081 HV The Netherlands J. Michael Young Department of Pharmacology University of Cambridge Tennis Court Road Cambridge CB2 1QJ UK