Therapeutic potential of 5-HT2C receptor ligands

TheScientificWorldJournal

Volumn 10, Issue , 2010, Pages 1870-1885

  Jensen, Nanna H ^a   Cremers, Thomas I ^b   Sotty, Florence ^a  

^a H LUNDBECK A S   (Denmark)

^b CHARLES RIVER LABORATORIES   (United States)

Author keywords

Anxiety; Depression; Dopamine; Obesity; Schizophrenia; Serotonin 5 HT2C receptors

Indexed keywords

(3 CHLOROPHENYL)PIPERAZINE; 1,2,3,4,8,9,10,10A OCTAHYDRO 7BH CYCLOPENTA[B][1,4]DIAZEPINO[6,7,1 HI]INDOLE; 1,2,3,5 TETRAHYDRO 5 METHYL 1 (3 PYRIDYLCARBAMOYL)PYRROLO[2,3 F]INDOLE; 2 (4,4,7 TRIMETHYL 1,4 DIHYDROINDENO[1,2 B]PYRROL 1 YL) 1 METHYLETHYLAMINE; 2 (6 CHLORO 5 FLUORO 1 INDOLYL) 1 METHYLETHYLAMINE; 5 METHYL 1 [[2 [(2 METHYL 3 PYRIDYL)OXY] 5 PYRIDYL]CARBAMOYL] 6 TRIFLUOROMETHYLINDOLINE; 6 CHLORO 5 METHYL 1 [[2 [(2 METHYL 3 PYRIDYL)OXY] 5 PYRIDYL]CARBAMOYL]INDOLINE; 8,9 DICHLORO 2,3,4,4A TETRAHYDRO 1H PYRAZINO[1,2 A]QUINOXALIN 5(6H) ONE; AGOMELATINE; ANTIDEPRESSANT AGENT; BVT 933; CP 809101; G PROTEIN COUPLED RECEPTOR; LIGAND; LORCASERIN; MESSENGER RNA; N PYRIDIN 3 YL 1,2 DIHYDRO 3H BENZO[E]INDOLE 3 CARBOXAMIDE; NEUROLEPTIC AGENT; RECEPTOR SUBTYPE; RO 60 0491; S 32006; SB 206533; SEROTONIN 2 AGONIST; SEROTONIN 2 ANTAGONIST; SEROTONIN 2B RECEPTOR; SEROTONIN 2C AGONIST; SEROTONIN 2C ANTAGONIST; SEROTONIN 2C RECEPTOR; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SEROTONIN RECEPTOR; SEROTONIN UPTAKE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VABICASERIN; SEROTONIN AGONIST; SEROTONIN ANTAGONIST;

ANXIETY DISORDER; BEHAVIOR; BRAIN; COGNITION; DEPRESSION; DOPAMINERGIC SYSTEM; DRUG MECHANISM; ENZYME ACTIVATION; EXTRAPYRAMIDAL SYMPTOM; GENE EXPRESSION; HUMAN; LIMBIC SYSTEM; MAJOR DEPRESSION; MEMORY; MOOD; MOOD DISORDER; NEUROPHARMACOLOGY; NEUROTRANSMISSION; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; OBESITY; PSYCHOSIS; RECEPTOR BLOCKING; REVIEW; RNA EDITING; SCHIZOPHRENIA; SEROTONINERGIC SYSTEM; SIDE EFFECT; SIGNAL TRANSDUCTION; SYMPTOM; TRANQUILIZING ACTIVITY; WEIGHT GAIN; ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; DRUG POTENTIATION; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; COGNITION; HUMANS; MOOD DISORDERS; OBESITY; RECEPTOR, SEROTONIN, 5-HT2C; SCHIZOPHRENIA; SEROTONIN AGONISTS; SEROTONIN ANTAGONISTS; SIGNAL TRANSDUCTION;

EID: 78349265354     PISSN: None     EISSN: 1537744X     Source Type: Journal    
DOI: 10.1100/tsw.2010.180     Document Type: Review

References (124)

1. Dawson, L.A. and Bromidge, S.M. (2008) 5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders. Curr. Top. Med. Chem. 8, 1008-1023.
2. Green, A. R. (2006) Neuropharmacology of 5-hydroxytryptamine. Br. J. Pharmacol. 147, S145-S152.
3. Hoyer, D., Hannon, J.P., and Martin, G.R. (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol. Biochem. Behav. 71, 533-554.
4. Roth, B.L., Willins, D.L., Kristiansen, K., and Kroeze, W.K. (1998) 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol. Ther. 79, 231-257.
5. Vertes, R.P., Linley, S.B., and Hoover, W.B. (2010) Pattern of distribution of serotonergic fibers to the thalamus of the rat. Brain Struct. Funct. 215, 1-28.
6. Adell, A., Celada, P., Abellan, M.T., and Artigas, F. (2002) Origin and functional role of the extracellular serotonin in the midbrain raphe nuclei. Brain Res. Rev. 39, 154-180. (Pubitemid 35341097)
7. Kroeze, W.K. and Roth, B.L. (1998) The molecular biology of serotonin receptors: therapeutic implications for the interface of mood and psychosis. Biol. Psychiatry 44, 1128-1142.
8. Fink, K.B. and Gothert, M. (2007) 5-HT receptor regulation of neurotransmitter release. Pharmacol. Rev. 59, 360-417.
9. Alex, K.D. and Pehek, E.A. (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol. Ther. 113, 296-320.
10. Clemett, D.A., Punhani, T., Duxon, M.S., Blackburn, T.P., and Fone, K.C. (2000) Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS. Neuropharmacology 39, 123-132.
11. Leysen, J.E. (2004) 5-HT2 receptors. Curr. Drug Targets CNS Neurol. Disord. 3, 11-26.
12. Navailles, S., Moison, D., Cunningham, K.A., and Spampinato, U. (2008) Differential regulation of the mesoaccumbens dopamine circuit by serotonin2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine. Neuropsychopharmacology 33, 237-246.
13. Serrats, J., Mengod, G., and Cortes, R. (2005) Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei. J. Chem. Neuroanat. 29, 83-91.
14. Eberle-Wang, K., Mikeladze, Z., Uryu, K., and Chesselet, M.F. (1997) Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats. J. Comp. Neurol. 384, 233-247. (Pubitemid 27282041)
15. Invernizzi, R.W., Pierucci, M., Calcagno, E., Di Giovanni, G., Di Matteo, V, Benigno, A., and Esposito, E. (2007) Selective activation of 5-HT(2C) receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: a combined in vivo electrophysiological and neurochemical study. Neuroscience 144, 1523-1535. (Pubitemid 46138024)
16. Di Giovanni, G., Di Matteo, V., La Grutta, V., and Esposito, E. (2001) m-Chlorophenylpiperazine excites nondopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors. Neuroscience 103, 111-116. (Pubitemid 32304350)
17. Bubar, M.J. and Cunningham, K.A. (2007) Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience 146, 286-297.
18. Berg, K.A., Dunlop, J., Sanchez, T., Silva, M., and Clarke, W.P. (2008) A conservative, single-amino acid substitution in the second cytoplasmic domain of the human serotonin2C receptor alters both ligand-dependent and -independent receptor signaling. J. Pharmacol. Exp. Ther. 324, 1084-1092.
19. Burns, C.M., Chu, H., Rueter, S.M., Hutchinson, L.K., Canton, H., Sanders-Bush, E., and Emeson, R.B. (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387, 303-308. (Pubitemid 27220768)
20. Zhang, J.Y., Kowal, D.M., Nawoschik, S.P., Lou, Z., and Dunlop, J. (2006) Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Biochem. Pharmacol. 71, 521-529.
21. Fletcher, P.J., Sinyard, J., and Higgins, G.A. (2006) The effects of the 5-HT(2C) receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists. Psychopharmacology 187, 515-525.
22. Gurevich, I., Englander, M.T., Adlersberg, M., Siegal, N.B., and Schmauss, C. (2002) Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission. J. Neurosci. 22, 10529-10532.
23. Iwamoto, K., Nakatani, N., Bundo, M., Yoshikawa, T., and Kato, T. (2005) Altered RNA editing of serotonin 2C receptor in a rat model of depression. Neurosci. Res. 53, 69-76. (Pubitemid 41073729)
24. Porter, R.H., Benwell, K.R., Lamb, H., Malcolm, C.S., Allen, N.H., Revell, D.F., Adams, D.R., and Sheardown, M.J. (1999) Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br. J. Pharmacol. 128, 13-20.
25. Palfreyman, M.G., Schmidt, C.J., Sorensen, S.M., Dudley, M.W., Kehne, J.H., Moser, P., Gittos, M.W., and Carr, A.A. (1993) Electrophysiological, biochemical and behavioral evidence for 5-HT2 and 5-HT3 mediated control of dopaminergic function. Psychopharmacology 112, S60-S67.
26. Prisco, S., Pagannone, S., and Esposito, E. (1994) Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo. J. Pharmacol. Exp. Ther. 271, 83-90.
27. Di Giovanni, G., Di Matteo, V., Di Mascio, M., and Esposito, E. (2000) Preferential modulation of mesolimbic vs. nigrostriatal dopaminergic function by serotonin(2C/2B) receptor agonists: a combined in vivo electrophysiological and microdialysis study. Synapse 35, 53-61.
28. Di Matteo, V., Di Giovanni, G., Di Mascio, M., and Esposito, E. (1999) SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system. Neuropharmacology 38, 1195-1205.
29. Navailles, S., Moison, D., Ryczko, D., and Spampinato, U. (2006) Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors. J. Neurochem. 99, 1311-1319.
30. De Deurwaerdere P., Navailles, S., Berg, K.A., Clarke, W.P., and Spampinato, U. (2004) Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens. J. Neurosci. 24, 3235-3241.
31. Mueser, K.T. and McGurk, S.R. (2004) Schizophrenia. Lancet 363, 2063-2072.
32. Lang, U.E., Puls, I., Muller, D.J., Strutz-Seebohm, N., and Gallinat, J. (2007) Molecular mechanisms of schizophrenia. Cell Physiol. Biochem. 20, 687-702.
33. Wacker, D.A. and Miller, K.J. (2008) Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases. Curr. Opin. Drug Discov. Dev. 11, 438-445.
34. Marquis, K.L., Sabb, A.L., Logue, S.F., Brennan, J.A., Piesla, M.J., Comery, T.A., Grauer, S.M., Ashby, C.R., Jr., Nguyen, H.Q., Dawson, L.A., Barrett, J.E., Stack, G., Meltzer, H.Y., Harrison, B.L., and Rosenzweig-Lipson, S. (2007) WAY-163909[(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b] [1,4]diazepino[6,7,1hi]indole]: a novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity. J. Pharmacol. Exp. Ther. 320, 486-496.
35. Siuciak, J.A., Chapin, D.S., McCarthy, S.A., Guanowsky, V., Brown, J., Chiang, P., Marala, R., Patterson, T., Seymour, P.A., Swick, A., and Iredale, P.A. (2007) CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity. Neuropharmacology 52, 279-290.
36. Koob, G.F., Simon, H., Herman, J.P., and Le, M.M. (1984) Neuroleptic-like disruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigrostriatal dopamine systems. Brain Res. 303, 319-329.
37. Olsen, C.K., Brennum, L.T., and Kreilgaard, M. (2008) Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics. Eur. J. Pharmacol. 584, 318-327.
38. Wadenberg, M.L. and Hicks, P.B. (1999) The conditioned avoidance response test re-evaluated: is it a sensitive test for the detection of potentially atypical antipsychotics? Neurosci. Biobehav. Rev. 23, 851-862.
39. Kennett, G.A., Wood, M.D., Bright, F., Trail, B., Riley, G., Holland, V., Avenell, K.Y., Stean, T., Upton, N., Bromidge, S., Forbes, I.T., Brown, A.M., Middlemiss, D.N., and Blackburn, T.P. (1997) SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology 36, 609-620.
40. Martin, J.R., Bos, M., Jenck, F., Moreau, J., Mutel, V., Sleight, A.J., Wichmann, J., Andrews, J.S., Berendsen, H.H., Broekkamp, C.L., Ruigt, G.S., Kohler, C., and Delft, A.M. (1998) 5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential. J. Pharmacol. Exp. Ther. 286, 913-924.
41. Dunlop, J., Marquis, K.L., Lim, H.K., Leung, L., Kao, J., Cheesman, C., and Rosenzweig-Lipson, S. (2006) Pharmacological profile of the 5-HT(2C) receptor agonist WAY-163909; therapeutic potential in multiple indications. CNS Drug Rev. 12, 167-177.
42. Grace, A.A. (1992) The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia. J. Neural Transm. Suppl. 36, 91-131.
43. Kapur, S. and Remington, G. (1996) Serotonin-dopamine interaction and its relevance to schizophrenia. Am. J. Psychiatry 153, 466-476.
44. Calcagno, E., Carli, M., Baviera, M., and Invernizzi, R.W. (2009) Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockade. J. Neurochem. 108, 521-532.
45. McLean, S.L., Woolley, M.L., Thomas, D., and Neill, J.C. (2009) Role of 5-HT receptor mechanisms in subchronic PCP-induced reversal learning deficits in the rat. Psychopharmacology 206, 403-414.
46. Boulougouris, V. and Robbins, T.W. (2010) Enhancement of spatial reversal learning by 5-HT2C receptor antagonism is neuroanatomically specific. J. Neurosci. 30, 930-938.
47. Millan, M.J., Dekeyne, A., and Gobert, A. (1998) Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not 5-HT, release in the frontal cortex in vivo. Neuropharmacology 37, 953-955.
48. Pozzi, L., Acconcia, S., Ceglia, I., Invernizzi, R.W., and Samanin, R. (2002) Stimulation of 5-hydroxytryptamine (5-HT(2C) ) receptors in the ventrotegmental area inhibits stress-induced but not basal dopamine release in the rat prefrontal cortex. J. Neurochem. 82, 93-100.
49. Robinson, E.S., Dalley, J.W., Theobald, D.E., Glennon, J.C., Pezze, M.A., Murphy, E.R., and Robbins, T.W. (2008) Opposing roles for 5-HT2A and 5-HT2C receptors in the nucleus accumbens on inhibitory response control in the 5-choice serial reaction time task. Neuropsychopharmacology 33, 2398-2406.
50. Fletcher, P.J., Tampakeras, M., Sinyard, J., and Higgins, G.A. (2007) Opposing effects of 5-HT(2A) and 5-HT(2C) receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test. Psychopharmacology (Berl.) 195, 223-234.
51. Baune, B.T., Adrian, I., and Jacobi, F. (2007) Medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population. J. Psychosom. Res. 62, 109-118.
52. Kessler, R.C., Akiskal, H.S., Ames, M., Birnbaum, H., Greenberg, P., Hirschfeld, R.M., Jin, R., Merikangas, K.R., Simon, G.E., and Wang, P.S. (2006) Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers. Am. J. Psychiatry 163, 1561-1568.
53. Katz, M.M., Maas, J.W., Frazer, A., Koslow, S.H., Bowden, C.L., Berman, N., Swann, A.C., and Stokes, P.E. (1994) Drug-induced actions on brain neurotransmitter systems and changes in the behaviors and emotions of depressed patients. Neuropsychopharmacology 11, 89-100.
54. Bowden, C.L., Koslow, S.H., Hanin, I., Maas, J.W., Davis, J.M., and Robins, E. (1985) Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid. Clin. Pharmacol. Ther. 37, 316-324.
55. Akimova, E., Lanzenberger, R., and Kasper, S. (2009) The serotonin-1A receptor in anxiety disorders. Biol. Psychiatry 66, 627-635.
56. Machado-Vieira, R., Salvadore, G., Luckenbaugh, D.A., Manji, H.K., and Zarate, C.A., Jr. (2008) Rapid onset of antidepressant action: a new paradigm in the research and treatment of major depressive disorder. J. Clin. Psychiatry 69, 946-958.
57. Henkel, V., Seemuller, F., Obermeier, M., Adli, M., Bauer, M., Mundt, C., Brieger, P., Laux, G., Bender, W., Heuser, I., Zeiler, J., Gaebel, W., Mayr, A., Moller, H.J., and Riedel, M. (2009) Does early improvement triggered by antidepressants predict response/remission? Analysis of data from a naturalistic study on a large sample of inpatients with major depression. J. Affect. Disord. 115, 439-449.
58. Cassano, P. and Fava, M. (2004) Tolerability issues during long-term treatment with antidepressants. Ann. Clin. Psychiatry 16, 15-25.
59. Millan, M.J. (2009) Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs. Neurotherapeutics 6, 53-77.
60. Bristow, L.J., O'Connor, D., Watts, R., Duxon, M.S., and Hutson, P.H. (2000) Evidence for accelerated desensitisation of 5-HT(2C) receptors following combined treatment with fluoxetine and the 5-HT(1A) receptor antagonist, WAY 100,635, in the rat. Neuropharmacology 39, 1222-1236.
61. Kennett, G.A., Lightowler, S., de Biasi, V., Stevens, N.C., Wood, M.D., Tulloch, I.F., and Blackburn, T.P. (1994) Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function. Neuropharmacology 33, 1581-1588.
62. Griebel, G., Perrault, G., and Sanger, D.J. (1997) A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety. Neuropharmacology 36, 793-802.
63. Murphy, D.L., Mueller, E.A., Hill, J.L., Tolliver, T.J., and Jacobsen, F.M. (1989) Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology 98, 275-282.
64. Silverstone, P.H., Rue, J.E., Franklin, M., Hallis, K., Camplin, G., Laver, D., and Cowen, P.J. (1994) The effects of administration of mCPP on psychological, cognitive, cardiovascular, hormonal and MHPG measurements in human volunteers. Int. Clin. Psychopharmacol. 9, 173-178.
65. Cryan, J.F. and Lucki, I. (2000) Antidepressant-like behavioral effects mediated by 5-hydroxytryptamine(2C) receptors. J. Pharmacol. Exp. Ther. 295, 1120-1126.
66. Marsden, C.A. and Stanford, S.C. (2000) CNS drugs III: psychotherapeutics. Expert Opin. Investig. Drugs 9, 1923-1929.
67. Rosenzweig-Lipson, S., Sabb, A., Stack, G., Mitchell, P., Lucki, I., Malberg, J.E., Grauer, S., Brennan, J., Cryan, J.F., Sukoff Rizzo, S.J., Dunlop, J., Barrett, J.E., and Marquis, K.L. (2007) Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents. Psychopharmacology 192, 159-170.
68. Dremencov, E., Newman, M.E., Kinor, N., Blatman-Jan, G., Schindler, C.J., Overstreet, D.H., and Yadid, G. (2005) Hyperfunctionality of serotonin-2C receptor-mediated inhibition of accumbal dopamine release in an animal model of depression is reversed by antidepressant treatment. Neuropharmacology 48, 34-42.
69. Yamauchi, M., Tatebayashi, T., Nagase, K., Kojima, M., and Imanishi, T. (2004) Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats. Pharmacol. Biochem. Behav. 78, 683-689.
70. Di Matteo, V., Cacchio, M., Di Giulio, C., and Esposito, E. (2002) Role of serotonin(2C) receptors in the control of brain dopaminergic function. Pharmacol. Biochem. Behav. 71, 727-734.
71. Bymaster, F.P., McNamara, R.K., and Tran, P.V. (2003) New approaches to developing antidepressants by enhancing monoaminergic neurotransmission. Expert Opin. Investig. Drugs 12, 531-543.
72. Shirayama, Y. and Chaki, S. (2006) Neurochemistry of the nucleus accumbens and its relevance to depression and antidepressant action in rodents. Curr. Neuropharmacol. 4, 277-291.
73. Martin-Soelch, C. (2009) Is depression associated with dysfunction of the central reward system? Biochem. Soc. Trans. 37, 313-317.
74. Dremencov, E., El Mansari, M., and Blier, P. (2009) Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area. J. Psychiatry Neurosci. 34, 223-229.
75. Calcagno, E., Guzzetti, S., Canetta, A., Fracasso, C., Caccia, S., Cervo, L., and Invernizzi, R.W. (2009) Enhancement of cortical extracellular 5-HT by 5-HT1A and 5-HT2C receptor blockade restores the antidepressant-like effect of citalopram in non-responder mice. Int. J. Neuropsychopharmacol. 12, 793-803.
76. Boothman, L., Raley, J., Denk, F., Hirani, E., and Sharp, T. (2006) In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a GABAergic mechanism. Br. J. Pharmacol. 149, 861-869. (Pubitemid 44851710)
77. Cremers, T.I., Rea, K., Bosker, F.J., Wikstrom, H.V., Hogg, S., Mork, A., and Westerink, B.H. (2007) Augmentation of SSRI effects on serotonin by 5-HT2C antagonists: mechanistic studies. Neuropsychopharmacology 32, 1550-1557. (Pubitemid 46920163)
78. Cremers, T.I., Giorgetti, M., Bosker, F.J., Hogg, S., Arnt, J., Mork, A., Honig, G., Bogeso, K.P., Westerink, B.H., den Boer, H., Wikstrom, H.V., and Tecott, L.H. (2004) Inactivation of 5-HT(2C) receptors potentiates consequences of serotonin reuptake blockade. Neuropsychopharmacology 29, 1782-1789.
79. Blier, P. (2001) Pharmacology of rapid-onset antidepressant treatment strategies. J. Clin. Psychiatry 62(Suppl 15), 12-17.
80. Piñeyro, G. and Blier, P. (1999) Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol. Rev. 51, 533-591.
81. Sotty, F., Folgering, J.H., Brennum, L.T., Hogg, S., Mork, A., Hertel, P., and Cremers, T.I. (2009) Relevance of dorsal raphe nucleus firing in serotonin 5-HT(2C) receptor blockade-induced augmentation of SSRIs effects. Neuropharmacology 57, 18-24.
82. Dekeyne, A., Mannoury la Cour, C., Gobert, A., Brocco, M., Lejeune, F., Serres, F., Sharp, T., Daszuta, A., Soumier, A., Papp, M., Rivet, J.M., Flik, G., Cremers, T.I., Muller, O., Lavielle, G., and Millan, M.J. (2008) S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models. Psychopharmacology 199, 549-568.
83. den Boer, J.A., Bosker, F.J., and Meesters, Y. (2006) Clinical efficacy of agomelatine in depression: the evidence. Int. Clin. Psychopharmacol. 21(Suppl 1), S21-S24.
84. Millan, M.J., Gobert, A., Lejeune, F., Dekeyne, A., Newman-Tancredi, A., Pasteau, V., Rivet, J.M., and Cussac, D. (2003) The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J. Pharmacol. Exp. Ther. 306, 954-964. (Pubitemid 37025301)
85. Millan, M.J., Lejeune, F., and Gobert, A. (2000) Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents. J. Psychopharmacol. 14, 114-138.
86. Schlag, B.D., Lou, Z., Fennell, M., and Dunlop, J. (2004) Ligand dependency of 5-hydroxytryptamine 2C receptor internalization. J. Pharmacol. Exp. Ther. 310, 865-870.
87. Stout, B.D., Clarke, W.P., and Berg, K.A. (2002) Rapid desensitization of the serotonin(2C) receptor system: effector pathway and agonist dependence. J. Pharmacol. Exp. Ther. 302, 957-962.
88. Fone, K.C., Austin, R.H., Topham, I.A., Kennett, G.A., and Punhani, T. (1998) Effect of chronic m-CPP on locomotion, hypophagia, plasma corticosterone and 5-HT2C receptor levels in the rat. Br. J. Pharmacol. 123, 1707-1715.
89. Banasr, M., Hery, M., Printemps, R., and Daszuta, A. (2004) Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29, 450-460.
90. Millan, M.J. (2005) Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie 60, 441-460.
91. Bagdy, G., Graf, M., Anheuer, Z.E., Modos, E.A., and Kantor, S. (2001) Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635. Int. J. Neuropsychopharmacol. 4, 399-408. (Pubitemid 33151684)
92. Overstreet, D.H., Knapp, D.J., Moy, S.S., and Breese, G.R. (2003) A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats. Psychopharmacology 167, 344-352.
93. Stein, D.J., Ahokas, A.A., and de Bodinat, C. (2008) Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J. Clin. Psychopharmacol. 28, 561-566.
94. Millan, M.J., Brocco, M., Gobert, A., and Dekeyne, A. (2005) Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology 177, 448-458.
95. Nunes-de-Souza, V., Nunes-De-Souza, R.L., Rodgers, R.J., and Canto-de-Souza, A. (2008) 5-HT2 receptor activation in the midbrain periaqueductal grey (PAG) reduces anxiety-like behaviour in mice. Behav. Brain Res. 187, 72-79. (Pubitemid 350216191)
96. Heisler, L.K., Zhou, L., Bajwa, P., Hsu, J., and Tecott, L.H. (2007) Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes Brain Behav. 6, 491-496.
97. Low, S., Chin, M.C., and Deurenberg-Yap, M. (2009) Review on epidemic of obesity. Ann. Acad. Med. Singapore 38, 57-59.
98. Smith, B.M., Thomsen, W.J., and Grottick, A.J. (2006) The potential use of selective 5-HT2C agonists in treating obesity. Expert Opin. Investig. Drugs 15, 257-266.
99. Heisler, L.K., Cowley, M.A., Tecott, L.H., Fan, W., Low, M.J., Smart, J.L., Rubinstein, M., Tatro, J.B., Marcus, J.N., Holstege, H., Lee, C.E., Cone, R.D., and Elmquist, J.K. (2002) Activation of central melanocortin pathways by fenfluramine. Science 297, 609-611.
100. Fitzgerald, L.W., Burn, T.C., Brown, B.S., Patterson, J.P., Corjay, M.H., Valentine, P.A., Sun, J.H., Link, J.R., Abbaszade, I., Hollis, J.M., Largent, B.L., Hartig, P.R., Hollis, G.F., Meunier, P.C., Robichaud, A.J., and Robertson, D.W. (2000) Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol. Pharmacol. 57, 75-81.
101. Rothman, R.B., Baumann, M.H., Savage, J.E., Rauser, L., McBride, A., Hufeisen, S.J., and Roth, B.L. (2000) Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102, 2836-2841.
102. Vickers, S.P., Dourish, C.T., and Kennett, G.A. (2001) Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 41, 200-209.
103. Vickers, S.P., Clifton, P.G., Dourish, C.T., and Tecott, L.H. (1999) Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology 143, 309-314.
104. Clifton, P.G., Lee, M.D., and Dourish, C.T. (2000) Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist and d-fenfluramine on feeding patterns in the rat. Psychopharmacology 152, 256-267.
105. Tecott, L.H., Sun, L.M., Akana, S.F., Strack, A.M., Lowenstein, D.H., Dallman, M.F., and Julius, D. (1995) Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374, 542-546.
106. Akana, S.F. (2008) Feeding and stress interact through the serotonin 2C receptor in developing mice. Physiol. Behav. 94, 569-579.
107. Nonogaki, K., Strack, A.M., Dallman, M.F., and Tecott, L.H. (1998) Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med. 4, 1152-1156. (Pubitemid 28468828)
108. Vickers, S.P., Easton, N., Webster, L.J., Wyatt, A., Bickerdike, M.J., Dourish, C.T., and Kennett, G.A. (2003) Oral administration of the 5-HT2Creceptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia. Psychopharmacology 167, 274-280.
109. Walsh, A.E., Smith, K.A., Oldman, A.D., Williams, C., Goodall, E.M., and Cowen, P.J. (1994) m-Chlorophenylpiperazine decreases food intake in a test meal. Psychopharmacology 116, 120-122.
110. Sargent, P.A., Sharpley, A.L., Williams, C., Goodall, E.M., and Cowen, P.J. (1997) 5-HT2C receptor activation decreases appetite and body weight in obese subjects. Psychopharmacology 133, 309-312.
111. Dunlop, J., Sabb, A.L., Mazandarani, H., Zhang, J., Kalgaonker, S., Shukhina, E., Sukoff, S., Vogel, R.L., Stack, G., Schechter, L., Harrison, B.L., and Rosenzweig-Lipson, S. (2005) WAY-163909[(7bR, 10aR)-1,2,3,4,8,9,10,10a- octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1h i]indole], a novel 5-hydroxytryptamine 2C receptor-selective agonist with anorectic activity. J. Pharmacol. Exp. Ther. 313, 862-869.
112. Lam, D.D., Przydzial, M.J., Ridley, S.H., Yeo, G.S., Rochford, J.J., O'Rahilly, S., and Heisler, L.K. (2008) Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 149, 1323-1328.
113. Rosenzweig-Lipson, S., Zhang, J., Mazandarani, H., Harrison, B.L., Sabb, A., Sabalski, J., Stack, G., Welmaker, G., Barrett, J.E., and Dunlop, J. (2006) Antiobesity-like effects of the 5-HT2C receptor agonist WAY-161503. Brain Res. 1073-1074, 240-251.
114. Thomsen, W.J., Grottick, A.J., Menzaghi, F., Reyes-Saldana, H., Espitia, S., Yuskin, D., Whelan, K., Martin, M., Morgan, M., Chen, W., Al-Shamma, H., Smith, B., Chalmers, D., and Behan, D. (2008) Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther. 325, 577-587.
115. Wacker, D.A., Varnes, J.G., Malmstrom, S.E., Cao, X., Hung, C.P., Ung, T., Wu, G., Zhang, G., Zuvich, E., Thomas, M.A., Keim, W.J., Cullen, M.J., Rohrbach, K.W., Qu, Q., Narayanan, R., Rossi, K., Janovitz, E., Lehman-McKeeman, L., Malley, M.F., Devenny, J., Pelleymounter, M.A., Miller, K.J., and Robl, J.A. (2007) Discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7- trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a selective, orally active agonist of the 5-HT(2C) receptor. J. Med. Chem. 50, 1365-1379. (Pubitemid 46496335)
116. Heisler, L.K., Cowley, M.A., Kishi, T., Tecott, L.H., Fan, W., Low, M.J., Smart, J.L., Rubinstein, M., Tatro, J.B., Zigman, J.M., Cone, R.D., and Elmquist, J.K. (2003) Central serotonin and melanocortin pathways regulating energy homeostasis. Ann. N. Y. Acad. Sci. 994, 169-174.
117. Xu, Y., Jones, J.E., Kohno, D., Williams, K.W., Lee, C.E., Choi, M.J., Anderson, J.G., Heisler, L.K., Zigman, J.M., Lowell, B.B., and Elmquist, J.K. (2008) 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron 60, 582-589.
118. Smith, B.M., Smith, J.M., Tsai, J.H., Schultz, J.A., Gilson, C.A., Estrada, S.A., Chen, R.R., Park, D.M., Prieto, E.B., Gallardo, C.S., Sengupta, D., Dosa, P.I., Covel, J.A., Ren, A., Webb, R.R., Beeley, N.R., Martin, M., Morgan, M., Espitia, S., Saldana, H.R., Bjenning, C., Whelan, K.T., Grottick, A.J., Menzaghi, F., and Thomsen, W.J. (2008) Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J. Med. Chem. 51, 305-313.
119. Halford, J.C., Harrold, J.A., Lawton, C.L., and Blundell, J.E. (2005) Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr. Drug Targets 6, 201-213.
120. Kennett, G.A. and Curzon, G. (1988) Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br. J. Pharmacol. 94, 137-147.
121. Forbes, I.T., Ham, P., Booth, D.H., Martin, R.T., Thompson, M., Baxter, G.S., Blackburn, T.P., Glen, A., Kennett, G.A., and Wood, M.D. (1995) 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. 38, 2524-2530.
122. Bromidge, S.M., Dabbs, S., Davies, D.T., Davies, S., Duckworth, D.M., Forbes, I.T., Gaster, L.M., Ham, P., Jones, G.E., King, F.D., Mulholland, K.R., Saunders, D.V., Wyman, P.A., Blaney, F.E., Clarke, S.E., Blackburn, T.P., Holland, V., Kennett, G.A., Lightowler, S., Middlemiss, D.N., Trail, B., Riley, G.J., and Wood, M.D. (2000) Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: identification of 5-methyl-1-[[2-[(2-methyl- 3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent. J. Med. Chem. 43, 1123-1134.
123. Dunlop, J., Zhang, G., Watts, S., Ramamoorthy, S., Harrison, B., Barrett, J., Magolda, R., Schechter, L., Pangalos, M.N., Stack, G., and Rosenzweig-Lipson, S. (2006) In vitro Pharmacological Profile of SCA-136, a Novel 5-HT2C Receptor Selective Agonist. 36th Annual Meeting for the Society of Neuroscience, Atlanta. Abstract.
124. Zupancic, M. and Guilleminault, C. (2006) Agomelatine: a preliminary review of a new antidepressant. CNS Drugs 20, 981-992.