Serotonin Receptor Subtypes and Ligands

Richard A. Glennon, Malgorzata Dukat and Richard B. Westkaemper

Department of Medicinal Chemistry
School of Pharmacy
Medical College of Virginia
Virginia Commonwealth University
Richmond Virginia 23298-0540.



1. Adham N, Vaysse PJ-J, Weinshank RL, Branchek TA. The cloned human 5-HT1E receptor couples to inhibition and activation of adenylyl cyclase via two distinct pathways in transfected BS-C-1 cells. Neuropharmacology 1994;33:403-410.

2. Adham N, Kao HT, Schechter LE, et al. Cloning of another human serotonin receptor (5-HT1F): A fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci USA 1993;90:408-412.

3. Adham N, Tamm JA, Salon JA, Vaysse PJJ, Weinshank RL, Branchek TA. A single point mutation increases the affinity of serotonin 5-HT1Da, 5-HT1Db, 5-HT1E and 5-HT1F receptors for b-adrenergic antagonists. Neuropharmacology 1994;33:387-391.

4. Adham N, Gerald C, Schechter L, Vaysse P, Weinshank R, Branchek T. [3H]5-Hydroxytryptamine labels the agonist high affinity state of the cloned rat 5-HT4 receptor. Eur J Pharmacol 1996;304:231-235.

5. Aghajanian GK. Electrophysiology of serotonin receptor subtypes and signal transduction pathways. In: Bloom FE, Kupfer DJ, ed. Psychopharmacology: The fourth generation of progress. New York: Raven Press, 1995;451-460.

6. Amlaiky N, Ramboz S, Boschert U, Plassat J-L, Hen R. Isolation of a mouse 5-HT1E-like serotonin receptor expressed predominantly in hippocampus. J Biol Chem 1992;267:19761-19764.

7. Anzini M, Cappelli A, Vomero S, et al. Novel, potent, and selective 5-HT3 receptor antagonists based on the arylpiperazine skeleton: Synthesis, structure, biological activity, and comparative molecular field analysis studies. J Med Chem 1995;38:2692-2704.

8. Arborelius L, Nomikos GG, Hertel P, et al. The 5-HT1A receptor antagonist (S)-UH-301 augments the increase in extracellular concentrations of 5-HT in the frontal cortex produced by both acute and chronic treatment with citalopram. Naunyn-Schmiedebergs Arch Pharmacol 1996;353:630-640.

9. Assie M-B, Koek W. Effects of 5-HT1A receptor antagonists on hippocampal 5-hydtroxytryptamine levels: (S)-WAY100135, but not WAY100635, has partial agonist properties. Eur J Pharmacol 1996;304:15-21.

10. Audia JE, Evrard DA, Murdoch GR, et al. Potent, selective tetrahydro-b-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus. J Med Chem 1996;39:2773-2780.

11. Azmitia EC, Whitaker-Azmitia PM. Anatomy, cell biology and plasticity of the serotonergic system: Neuropsychopharmacological implications for the actions of psychotropic drugs. In: Bloom FE, Kupfer DJ, ed. Psychopharmacology: The fourth generation of progress. New York: Raven Press, 1995;443-449.

12. Bakthavachalam V, Fell B, Teitler M, Glennon RA, Neumeyer JL. Fluorescent probes for serotonin 5-HT1A receptors: Synthesis, receptor affinity and selectivity. Med Chem Res 1991;1:265-276.

13. Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL. Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem 1993;268:23422-23426.

14. Baxter GS. Novel discriminatory ligands for 5-HT2B receptors. Behav Brain Res 1996;73:149-152.

15. Belelli D, Balcarek JM, Hope AG, Peters JA, Lambert JJ, Blackburn TP. Cloning and functional expression of a human 5-hydroxytryptamine type 3As receptor subunit. Mol Pharmacol 1995;48:1054-1062.

16. Berardi F, Colabufo NA, Giudice G, et al. New s and 5-HT1A receptor ligands: w-(tetralin-1-yl)-n-alkylamine derivatives. J Med Chem 1996;39:176-182.

17. Boess FG, Martin IL. Molecular biology of 5-HT receptors. Neuropharmacology 1994;33:275-317.

18. Bonhaus DW, Bach C, DeSouza A, et al. The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol 1995;115:622-628.

19. Bouchelet I, Cohen Z, Case B, Seguela P, Hamel E. Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganGlia and cerebral blood vessels. Mol Pharmacol 1996;50:219-223.

20. Bourson A, Borroni E, Austin RH, Monsma FJ, Sleight AJ. Determination of the role of 5-HT6 receptors in the rat brain: A study using antisense oligonucleotides. J Pharmacol Exp Ther 1995;274:173-180.

21. Bourson A, Wanner D, Wyler R, et al. Pharmacologic evaluation of the discriminative stimulus of meta-chlorophenylpiperazine. Pharmacol Biochem Behav 1996;53:107-114.

22. Branchek T. Site-directed mutagenesis of serotonin receptors. Med Chem Res 1993;3:287-296.

23. Buchheit K-H, Gamse R, Giger R, et al. The serotonin 5-HT4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists. J Med Chem 1995;38:2331-2338.

24. Callahan PM, Cunningham KA. Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Eur J Pharmacol 1994;257:27-38.

25. Carson MJ, Thomas EA, Danielson PE, Sutcliffe JG. The 5-HT5A serotonin receptor is expressed predominantly by astrocytes in which it inhibits cAMP accumulation: A mechanism for neuronal suppression of reactive astrocytes. Glia 1996;17:317-326.

26. Choi D-S, Loric S, Colas J-F, et al. The mouse 5-HT2B receptor: homologous subtype or species variant? Behav Brain Res 1996;73:253-257.

27. Choudhary MS, Sachs N, Ulver A, Glennon RA, Westkaemper RB, Roth BL. Differential ergoline and ergopeptine binding to 5-HT2A receptors: Ergolines require an aromatic residue at position 340 for high affinity. Mol Pharmacol 1995;47:450-457.

28. Clitherow JW, Scopes DIC, Skingle M J, et al. Evolution of [(N,N-dimethylamino)propyl]- and piperazinylbenzanilides as the first selective 5-HT1D antagonists.J Med Chem 1994;37:2253-2257.

29. Cushing DJ, Zgombick JM, Nelson DL, Cohen ML. LY215840, a high-affinity 5-HT7 receptor ligand blocks serotonin-induced relaxation in canine coronary artery. J Pharmacol Exp Ther 1996;277:1560-1566.

30. Darmani NA, Reeves SL. The mechanism by which the selective 5-HT1A receptor antagonist S(-)UH 301 produces head-twitches in mice. Pharmacol Biochem Behav 1996;55:1-10.

31. Demchyshyn L, Sunahara RK, Miller K, et al. A human serotonin 1D receptor variant (5-HT1Db) encoded by an intronless gene on chromosome 6. Proc Natl Acad Sci USA 1992;89:5522-5526.

32. De Vries P, Heiligers JPC, Villalon CM, Saxena PR. Blockade of porcine carotid vascular responses to sumatriptan by GR127935, a selective 5-HT1D receptor antagonist. Br J Pharmacol 1996;:118 85-92.

33. De Vry J. 5-HT1A receptor agonists: Recent developments and controversial issues. Psychopharmacology 1995;121:1-26.

34. Dillon KA, Gross-Isseroff R, Israeli M, Biegon A. Autoradiographic analysis of 5-HT1A receptor binding in the human brain postmortem: effect of age and alcohol. Brain Res 1991;554:56-64.

35. Doucet E, Pohl M, Fattaccini C-M, Adrien J, El Mestikawy S, Hamon, M. In situ hybridization evidence for the synthesis of 5-HT1B receptor in serotonergic neurons of anterior raphe nuclei in the rat brain. Synapse 1995;19:18-28.

36. Dukat M, Abdel-Rahman AA, Ismaiel AM, et al. Structure-activity relationships for the binding of arylpiperazines and arylbiguanides at 5-HT3 serotonin receptors. J Med Chem 1996, 39:4017-4035.

37. Eglen RM, Bonhaus DW, Clark RD, et al. (R) and (S) RS 56532: Mixed 5-HT3 and 5-HT4 receptor ligands with opposing enantiomeric selectivity. Neuropharmacology 1994;33:515-526.

38. Eglen RM, Wong EHF, Dumuis A, Bockaert J. Central 5-HT4 receptors. Trends Pharmacol Sci 1995;16:391-398.

39. File SE. Recent developments in anxiety, stress, and depression. Pharmacol Biochem Behav 1996;54:3-12 and following papers.

40. Fiorella D, Rabin RA, Winter JC. The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I. Antagonist correlation analysis. Psychopharmacology 1995;121:347-356.

41. Fletcher A, Cliffe I, Dourish CT. Silent 5-HT1A receptor antagonists: utility as research tools and therapeutic agents. Trends Pharmacol Sci 1993;14:441-448.

42. Forbes IT, Jones GE, Murphy OE, Holland V, Baxter GS. N-(1-Methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea: A novel, high-affinity 5-HT2B receptor antagonist. J Med Chem 1995;38:855-857.

43. Forbes IT, Ham P, Booth DH, et al. 5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: A novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity. J Med Chem 1995;38:2524-2530.

44. Gaster LM, Joiner GF, King FD, et al. N-[(1-Butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide hydrochloride: The first potent and selective 5-HT4 receptor antagonist with oral activity. J Med Chem 1995;38:4760-4763.

45. Gelernter J, Rao PA, Pauls DL, Hamblin MW, Sibley DR, Kidd KK. Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics 1995;26:207-209.

46. Gerald C, Adham N, Kao H-T, et al. The 5-HT4 receptor: molecular cloning and pharmacological classification of two splice variants. EMBO J 1995;14:2806-2815.

47. Glatt CE, Snowman A, Sibley DR, Snyder SH. Clozapine: selective labeling of sites resembling 5-HT6 serotonin receptors may reflect psychoactive profile. Mol Med 1995;1:398-406.

48. Glennon RA. Do hallucinogens act as 5-HT2 agonists or antagonists? Neuropsychopharmacology 1990;56:509-517.

49. Glennon RA. Concepts for the design of 5-HT1A serotonin agonists and antagonists. Drug Dev Res 1992;26:251-274.

50. Glennon RA, Dukat M. 5-HT receptor ligands—Update 1992. Curr Drugs Serotonin 1993;1:1-45.

51. Glennon RA, Dukat M. Serotonin receptor subtypes. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth generation of progress. New York: Raven Press, 1995;415-429.

52. Glennon RA, Westkaemper RB, Bartyzel P. Medicinal chemistry of serotonergic agents. In: Peroutka SJ, ed. Serotonin receptor subtypes. New York: Wiley-Liss, 1991;19-64.

53. Glennon RA, Westkaemper RB. 5-HT1D receptors: A serotonin receptor population for the 1990's. Drug News Perspect 1993, 6:390-405.

54. Glennon RA, Dukat M, Westkaemper RB, Ismaiel AM, Izzarelli DG, Parker EM. The binding of propranolol at 5-hydroxytryptamine1Db T355N mutant receptors may involve formation of two hydrogen bonds to asparagine. Mol Pharmacol 1996;49:198-206.

55. Gobbi M, Parotti L, Mennini T. Are 5-hydroxytryptamine7 receptors involved in [3H]5-hydroxytryptamine binding to 5-hydroxytryptamine1nonA-nonB receptors in rat hypothalamus? Mol Pharmacol 1996;49:556-559.

56. Greenshaw AJ. Behavioural pharmacology of 5-HT3 receptor antagonists: A critical update on therapeutic potential. Trends Pharmacol Sci 1993;14:265-270.

57. Griebel G, Blanchard DC, Rettori M-C, Guardiola-Lemaitre B, Blanchard RJ. Preclinical profile of the mixed 5-HT1A/5-HT2 receptor antagonist S 21357. Pharmacol Biochem Behav 1996;54:509-516.

58. Gudermann T, Levy FO, Birnbaumer M, Birnbaumer L, Kaumann AJ. Human S31 serotonin receptor clone encodes a 5-hydroxytryptamine1E-like serotonin receptor. Mol Pharmacol 1993;43:412-418.

59. Gustafson EL, Durkin MM, Bard JA, Zgombick J, Branchek TA. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain. Br J Pharmacol 1996;117:657-666.

60. Gyermek L. 5-HT3 receptors: Pharmacologic and therapeutic aspects. J Clin Pharmacol 1995;35:845-855.

61. Hamel E. 5-HT1D receptors: Pharmacology and therapeutic potential. Serotonin 1996;1:19-29.

62. Hartig PR, Branchek TA, Weinshank RL. A subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci 1992;13:152-159.

63. Harwood G, Lockyer M, Giles H, Fairweather N. Cloning and characterization of the rabbit 5-HT1Da and 5-HT1Db receptors. FEBS Lett 1995;377:73-76.

64. Herndon JL, Glennon RA. Serotonin receptors, agents, and actions. In: Kozikowsky A, ed. Drug design, molecular modeling, and the neurosciences. New York: Raven Press, 1993;167-212.

65. Hoyer D, Martin GR. Classification and nomenclature of 5-HT receptors: A comment on current issues. Behav Brain Res 1996;73:263-268.

66. Hoyer D, Clarke DE, Fozard JR, et al. International Union of Pharmacology Nomenclature and classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994;46:157-203.

67. Ismaiel AM, De Los Angeles J, Teitler M, Ingher S, Glennon RA. Antagonism of a 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- vs. 5-HT1C-selective antagonist. J Med Chem 1993;36:2519-2525.

68. Ismaiel AM, Dukat M, Nelson DL, Lucaites VL, Glennon RA. Binding of N2-substituted pyrido[4,3-b]indole analogs of spiperone at human 5-HT2A, 5-HT2B, and 5-HT2C serotonin receptors. Med Chem Res 1996;6:197-211.

69. Jin H, Oksenberg D, Ashkenazi A, et al. Characterization of the human 5-hydroxytryptamine-1B receptor. J Biol Chem 1992;267:5835-5838.

70. Kalkman HO. Is migraine prophylactic activity caused by 5-HT2B or 5-HT2C receptor blockade? Life Sci 1994;54:641-644.

71. Kennett GA, Wood MD, Grewal GS, Forbes I, Gadre A, Blackburn TP. In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. Br J Pharmacol 1994;111:797-802.

72. Kennett GA, Bailey F, Piper DC, Blackburn TP. Effect of SB 200646A, a 5-HT2C/5-HT2B antagonist in two conflict models of anxiety. Psychopharmacology 1995;118:178-182.

73. Kennett GA, Wood MD, Bright F, et al. In vitro and in vivo profile of SB 206553, a potent 5-HT2C/5-HT2B receptor antagonist with anxiolytic-like properties. Br J Pharmacol 1996;117:427-434.

74. King FD, Jones BJ, Sanger GJ, eds. 5-Hydroxytryptamine-3 receptor antagonists. Boca Raton: CRC Press, 1994.

75. Kohen R, Metcalf MA, Khan N, et al. Cloning, characterization and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem 1996;66:47-56.

76. Koek W, Jackson A, Colpaert FC. Behavioral pharmacology of antagonists at 5-HT2/5-HT1C receptors. Neurosci Biobehav Rev 1992;16:95-105.

77. Kuipers W, van Wijngaarden I, Ijzerman A P. A model of the serotonin 5-HT1A receptor: agonist and antagonist binding sites. Drug Design Discov 1994;11:231-249.

78. Kung M-P, Zhuang Z-P, Frederick D, Kung HF. In vivo binding of [123I]4-(2'methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-iodobenzamido]ethylpiperazine, p-MPPI, to 5-HT1A receptors in rat brain. Synapse 1994;18:359-366.

79. Leonhardt S, Herrick-Davis K, Titeler M. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: Interaction with a GTP-binding protein. J Neurochem 1989;53:465-471.

80. Levy FO, Gudermann T, Birnbaumer M, Kaumann AJ, Birnbaumer L. Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylate cyclase. FEBS Lett 1992;296:201-206.

81. Lin C-H, Haadsma-Svensson SR, Phillips G, et al. Synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9-carbozamide: A potent and selective 5-HT1A receptor agonist with good oral availability. J Med Chem 1993;36:2208-2218.

82. Liu Y, Yu H, Svensson BE, Cortizo L, Lewander T, Hacksell U. Derivatives of 2-(dipropylamino)tetralin: Effect of the C8-substituent on the interaction with 5-HT1A receptors. J Med Chem 1993;36:4221-4229.

83. Long TA, Kalmus GW, Bjork A, Myers RD. Alcohol intake in high alcohol drinking (HAD) rats is supressed by FG5865, a novel 5-HT1A agonist/5-HT2 antagonist. Pharmacol Biochem Behav 1996;53:33-40.

84. Lovenberg TW, Baron BM, de Lecea L, et al. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 1993;11:449-458.

85. Lucas JJ, Hen R. New players in the 5-HT receptor field: genes and knockouts. Trends Pharmacol Sci 1995;16:246-252.

86. Martin GR, Humphrey PPA. Receptors for 5-hydroxytryptamine: Current perspectives on classification and nomenclature. Neuropharmacology 1994;33:261-273.

87. Matsubara S, Arora RC, Meltzer HY. Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims. J Neural Transm 1991;85:181-194.

88. Matthes H, Boschert V, Amlaiky N, et al. Mouse 5-hydroxytryptamine-5A and 5-hydroxytryptamine-5B receptors define a new family of serotonin receptors: Cloning, functional expression, and chromosomal localization. Mol Pharmacol 1993;43:313-319.

89. McAllister G, Charlesworth A, Snodin C, et al. Molecular cloning of a serotonin receptor from human brain (5-HT1E): A fifth 5-HT1-like subtype. Proc Natl Acad Sci USA 1992;89:5517-5521.

90. Miyake A, Mochizuki S, Takemoto Y, Akuzawa S. Molecular cloning of human 5-hydroxytryptamine3 receptor: Heterogeneity in distribution and function among species. Mol Pharmacol 1995;48:407-416.

91. Mokrosz JL, Klodzinska A, Boksa J, Bojarski AJ, Duszynska B, Chojnacka-Wojcik E. Two derivatives of 1-(o-methoxyphenyl)piperazine with an opposite function at 5-HT1A receptors. Arch Pharmacology 1995;328:381-383.

92. Mokrosz JL, Deren-Wesolek A, Tatarczynska E, et al. 8-[4-[2-(1,2,3,4-Tetrahydroisoquinolinyl)]butyl]-8-azaspiro[4.5]decane-7,9-dione: A new 5-HT1A receptor ligand with the same activity profile as buspirone. J Med Chem 1996;39:1125-1129.

93. Monsma FJ, Shey Y, Ward RP, Hamblin MW, Sibley DR. Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 1993;43:320-327.

94. Monti JM, Monti D, Jantos H, Ponzoni A. Effects of selective activation of the 5-HT1B receptor with CP-94,253 on sleep and wakefulness in the rat. Neuropharmacology 1995;34:1647-1651.

95. Morain P, Abraham C, Portevin B, DeNanteuil G. Biguanide derivatives: Agonist pharmacology at 5-hydroxytryptamine type 3 receptors in vitro. Mol Pharmacol 1994;46:732-742.

96. Mundey MK, Fletcher A, Marsden CA. Effects of 8-OH DPAT and 5-HT1A antagonists WAY 100135 and WAY 100635 on guinea pig behaviour and dorsal raphe 5-HT neurone firing. Br J Pharmacol 1996;117:750-756.

97. Neckelmann D, Bjorkum AA, Bjorvatn B, Ursin R. Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram. Behav Brain Res 1996;75:159-168.

98. Nelson DL, Glennon RA, Wainscott DB. Comparison of the affinities of hallucinogenic phenylalkylamines at the cloned human 5-HT2A, 2B, and 2C receptors. Abstract 120, Third IUPHAR Satellite Meeting on Serotonin, Chicago, IL. July 30-August 3, 1994. p. 116.

99. Newman-Tancredi A, Chaput C, Verriele L, Millan, MJ. S 15535 and WAY 100,635 antagonize 5-HT-stimulated [35S]GTPgS binding at cloned human 5-HT1A receptors. Eur J Pharmacol 1996;307:107-111.

100. Norman MH, Minick DJ, Rigdon GC. Effect of linking bridge modifications on the antipsychotic profile of some phthalimide and isoindolinone derivatives. J Med Chem 1996;39:149-157.

101. Norman MH, Rigdon GC, Hall WR, Navas F. Structure-activity relationships of a series of substituted benzamides: Potent D2/5-HT2 antagonists and 5-HT1A agonists as neuroleptic agents. J Med Chem 1996;39:1172-1188.

102. Nozulak J, Kalkman HO, Floersheim P, Hoyer D, Schoeffter P, Buerki HR. (+)cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylindolo[1,7-bc][2,6]-naphthyridine: A 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity. J Med Chem 1995;38:28-33.

103. O'Neill MF, Fernandez AG, Palacios JM. GR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and the action of antidepressants in the mouse tail suspension test. Pharmacol Biochem Behav 1996;53:535-539.

104. Orjales A, Alonso-Cires L, Labeaga L, Corcostegui R. New (2-methoxyphenyl)piperazine derivatives as 5-HT1A receptor ligands with reduced a1-adrenergic activity. Synthesis and structure-activity relationships. J Med Chem 1995;38:1273-1277.

105. Panocka I, Ciccocioppo R, Polidori C, Pompei P, Massi M. The 5-HT4 receptor antagonist GR113808 reduces ethanol intake in alcohol-preferring rats. Pharmacol Biochem Behav 1995;52:255-259.

106. Pasqualetti M, Nardi I, Ladinsky H, Marazziti D, Cassano GB. Comparative anatomical distribution of serotonin 1A, 1Da, and 2A receptor mRNAs in human brain postmortem. Mol Brain Res 1996;39:223-233.

107. Peglion J-L, Canton H, Bervoets K, et al. Characterization of potent and selective antagonists at postsynaptic 5-HT1A receptors in a series of N4-substituted arylpiperazines. J Med Chem 1995;38:4044-4055.

108. Peroutka SJ. Serotonin receptors. In: Meltzer HY, ed. Psychopharmacology: The third generation of progress. New York: Raven Press, 1987;303-311.

109. Peroutka SJ. Molecular biology of serotonin (5-HT) receptors. Synapse 1994;18:241-260.

110. Peroutka SJ, Howell TA. The molecular evolution of G-protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology 1994;33:319-324.

111. Perregaard J, Sanchez C, Arnt J. Recent developments in anxiolytics. Curr Opin Ther Pat 1993;3:101-126.

112. Plassat J-L, Amlaiky N, Hen R. Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol 1993;44:229-236.

113. Ramboz S, Saudou F, Amara DA, et al. 5-HT1B receptor knock out—behavioral consequences. Behav Brain Res 1996;73:305-312.

114. Rault S, Lancelot J-C, Prunier H, et al. Novel selective and partial agonists of 5-HT3 receptors. Part 1. Synthesis and biological evaluation of piperazinopyrrolothienopyrazines. J Med Chem 1996;39:2068-2080.

115. Rausch JL, Ruegg R, Moeller FG. Gepirone as a 5-HT1A agonist in the treatment of major depression. Psychopharmacol Bull 1990;26:169-171.

116. Rees S, den Daas I, Foord S, et al. Cloning and characterization of human 5-HT5A serotonin receptor. FEBS Lett 1994;335:242-246.

117. Reitz AB, Bennett DJ, Blum PS, et al. A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/a1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem 1994;37:1060-1062.

118. Rinaldi-Carmona M, Congy C, Santucci V, et al. Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. J Pharmacol Exp Ther 1992;262:759-768.

119. Rinaldi-Carmona M, Congy C, Simiand J, et al. Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain. Mol Pharmacol 1992;43:84-89.

120. Rodgers RJ, Cole JC, Davies A. Antianxiety and behavioral suppressant actions of the novel 5-HT1A receptor agonist, flesinoxan. Pharmacol Biochem Behav 1994;48:959-963.

121. Roth BL, Craigo SC, Choudhary MS, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 1994;268:1403-1410.

122. Routledge C, Gurling J, Ashworth-Preece MA, Dourish CT. Differential effects of WAY-100135 on the decrease in 5-hydroxytryptamine release induced by buspirone and NAN-190. Eur J Pharmacol 1995;276:281-284.

123. Ruat M, Traiffort E, Arrang J-M, et al. A novel rat serotonin (5-HT6) receptor: molecular cloning, localization, and stimulation of cAMP accumulation. Biochim Biophys Acta 1993;193:268-276.

124. Ruat M, Traiffort E, Leurs R, et al. Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci USA 1993;90:8547-8551.

125. Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S. Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun 1991;181:1469-1478.

126. Sanders-Bush E, Canton H. Serotonin receptors: Signal transduction pathways. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The fourth generation of progress. New York: Raven Press, 1995; 431-441.

127. Saudou F, Hen R. 5-HT receptor subtypes: Molecular and functional diversity. Med Chem Res 1994;4:16-84.

128. Saxena P. Serotonin receptors: subtypes, functional responses and therapeutic relevance. Pharmacol Ther 1995;66:339-368.

129. Schmidt CJ, Black CK. The putative 5-HT3 agonist phenylbiguanide induces carrier-mediated release of [3H]dopamine. Eur J Pharmacol 1989;167:309-310.

130. Schoeffter P, Hoyer D. 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther 1991;252:387-395.

131. Schoeffter P, Hoyer D. Interaction of arylpiperazines with 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D receptors. Do discriminatory 5-HT1B receptor ligands exist? Naunyn-Schmiedeberg's Arch Pharmacol 1989;339:675-683.

132. Schreiber R, Brocco M, Millan MJ. Blockade of the discriminative stimulus effects of DOI by MDL 100,907 and the atypical antipsychotics clozapine and risperidone. Eur J Pharmacol 1994;264:99-102.

133. Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane induced head-twitches are mediated by 5-hydroxytryptamine (5-HT)2A receptors: Modulation by novel 5-HT2A/2C antagonists, D1 antagonists, and 5-HT1A agonists. J Pharmacol Exp Ther 1995;273:101-112.

134. Shen Y, Monsma FJ, Jr, Metcalf MA, Hamblin MW, Sibley DR. Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem 1993;268:18200-18204.

135. Shih JC, Chen KJ-S, Gallaher TK. Molecular biology of serotonin receptors. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The fourth generation of progress. New York: Raven Press, 1995;407-414.

136. Sipes TE, Geyer MA. Functional behavioral homology between rat 5-HT1B and guinea pig 5-HT1D receptors in the modulation of prepulse inhibition of startle. Psychopharmacology 1996;122:231-237.

137. Skingle M, Beattie DT, Scopes DIC, et al. GR127935: A potent and selective 5-HT1D receptor antagonist. Behav Brain Res 1996;73:157-161.

138. Sleight AJ, Pierce PA, Schmidt AW, Hekmatpanah CR, Peroutka SJ. The clinical utility of serotonin receptor active agents in neuropsychiatric disease. In: Peroutka SJ, ed. Serotonin receptor subtypes. New York: Wiley-Liss, 1991;211-227.

139. Sleight AJ, Carolo C, Petit N, Zwingelstein C, Bourson A. Identification of 5-hydroxytryptamine7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant treatment. Mol Pharmacol 1995;47:99-103.

140. Sleight AJ, Monsma FJ, Borroni E, Austin RH, Bourson A. Effects of altered 5-ht6 expression in the rat: functional studies using antisense oligonucleotides. Behav Brain Res 1996;73:245-248.

141. Stjernlof P, Gullme M, Elebring T, et al. (S)- and (R)-8-(Di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carboxaldehyde: A new class of orally active 5-HT1A receptor agonists. J Med Chem 1993;36:2059-2065.

142. Tecott LH, Sun LM, Akana SF, et al. Eating disorders and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 1995;374:542-546.

143. Terron JA. The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype. Br J Pharmacol 1996;118:1421-1428.

144. Tollefson GD, Lancaster SP, Montague-Clouse J. The association of buspirone and its metabolite 1-pyrimidinylpiperazine in the remission of comorbid anxiety with depressive features and alcohol dependency. Psychopharmacol Bull 1991;27:163-170.

145. Tsou A, Kosaka A, Bach C, et al. Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to adenylyl cyclase. J Neurochem 1994;63:456-464.

146. van Hooft JA, Vijverberg HPM. Selection of distinct conformational states of the 5-HT3 receptor by full and partial agonists. Br J Pharmacol 1996;117:839-846.

147. van Steen BJ, van Wijngaarden I, Tulp MTM, Soudijn W. A series of N4-imidoethyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine as 5-HT1A receptor ligands: Synthesis and structure-activity relationships. J Med Chem 1995;38:4303-4308.

148. Vernier P, Cardinaud B, Valdenaire O, Philippe H, Vincent J-D. An evolutionary view of drug-receptor interaction: The bioamine receptor family. Trends Pharmacol Sci 1995;16:375-381.

149. Wainscott DB, Cohen ML, Schenck KW, et al. Pharmacological characteristics of the newly cloned 5-hydroxytryptamine-2F receptor. Mol Pharmacol 1993;43:419-426.

150. Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL. Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: Evidence for species differences. J Pharmacol Exp Ther 1996;276:720-727.

151. Wardle KA, Bingham S, Ellis ES, et al. Selective and functional 5-hydroxytryptamine4 receptor antagonism by SB 207266. Br J Pharmacol 1996;118:665-670.

152. Westkaemper RBl. Serotonin receptors: Molecular genetics and molecular modeling. Med Chem Res 1993;3:269-418.

153. Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR. Human serotonin1D receptor is encoded by a subfamily of two distinct genes: 5-HT1Da and 5-HT1Db. Proc Natl Acad Sci USA 1992;89:3630-3634.

154. Wisden W, Parker EM, Mahle CD, et al. Cloning and characterization of the rat 5-HT5B receptor. FEBS Lett 1993;333:25-31.

155. Yu X-J, Waeber C, Castanon N, et al. 5-Carboxamidotryptamine, CP-122,288 and dihydroergotamine but not sumatriptan, CP-93,129 and serotonin-5-o-carboxymethylglycyltyrosinamide block dural plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine1B receptors. Mol Pharmacol 1996;49:761-765.

156. Zemlan FP, Schwab EF. Charaterization of a novel serotonin receptor subtype (5-HT1S) in rat CNS: Interaction with a GTP binding protein. J Neurochem 1991;57:2092-2099.

157. Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL. Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine-1E receptor. Mol Pharmacol 1992;42:180-185.

158. Zifa E, Fillion G. 5-Hydroxytryptamine receptors. Pharmacol Rev 1992;44:401-458.

Back to Chapter

published 2000