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Serotonin1A receptors in the pathophysiology of schizophrenia: development of novel cognition-enhancing therapeutics

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Abstract

Serotonin (5-HT) receptors have been suggested to play key roles in psychosis, cognition, and mood via influence on neurotransmitters, synaptic integrity, and neural plasticity. Specifically, genetic evidence indicates that 5-HT1A, 5-HT2A, and 5-HT2C receptor single-nucleotide polymorphisms (SNPs) are related to psychotic symptoms, cognitive disturbances, and treatment response in schizophrenia. Data from animal research suggest the role of 5-HT in cognition via its influence on dopaminergic, cholinergic, glutamatergic, and GABAergic function. This article provides up-to-date findings on the role of 5-HT receptors in endophenotypic variations in schizophrenia and the development of newer cognition-enhancing medications, based on basic science and clinical evidence. Imaging genetics studies on associations of polymorphisms of several 5-HT receptor subtypes with brain structure, function, and metabolism suggest a role for the prefrontal cortex and the parahippocampal gyrus in cognitive impairments of schizophrenia. Data from animal experiments to determine the effect of agonists/antagonists at 5-HT1A, 5-HT2A, and 5-HT2C receptors on behavioral performance in animal models of schizophrenia based on the glutamatergic hypothesis provide useful information. For this purpose, standard as well as novel cognitive tasks provide a measure of memory/information processing and social interaction. In order to scrutinize mixed evidence for the ability of 5-HT1A agonists/antagonists to improve cognition, behavioral data in various paradigms from transgenic mice overexpressing 5-HT1A receptors provide valuable insights. Clinical trials reporting the advantage of 5-HT1A partial agonists add to efforts to shape pharmacologic perspectives concerning cognitive enhancement in schizophrenia by developing novel compounds acting on 5-HT receptors. Overall, these lines of evidence from translational research will facilitate the development of newer pharmacologic strategies for the treatment of cognitive disturbances of schizophrenia.

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References

  1. Saykin AJ, Gur RC, Gur RE, et al. Neuropsychological function in schizophrenia: selective impairment in memory and learning. Arch Gen Psychiatry. 1991;48:618–624.

    PubMed  CAS  Google Scholar 

  2. Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology 8th Edition. Oxford: Oxford University Press; 2003.

    Google Scholar 

  3. Masellis M, Basile V, Meltzer HY, et al. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology. 1998;19:123–132.

    Article  PubMed  CAS  Google Scholar 

  4. Drago A, Ronchi DD, Serretti A. 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Int J Neuropsychopharmacol. 2008;11:701–721.

    Article  PubMed  CAS  Google Scholar 

  5. Meltzer HY, Li Z, Kaneda Y, Ichikawa J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:1159–1172.

    Article  PubMed  CAS  Google Scholar 

  6. Sumiyoshi T, Anil AE, Jin D, Jayathilake K, Lee M, Meltzer HY. Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int J Neuropsychopharmacol. 2004;7:1–8.

    Article  PubMed  CAS  Google Scholar 

  7. Sumiyoshi T, Jin D, Jayathilake K, Lee M, Meltzer HY. Prediction of the ability of clozapine to treat negative symptoms from plasma glycine and serine levels in schizophrenia. Int J Neuropsychopharmacol. 2005;8:451–455.

    Article  PubMed  CAS  Google Scholar 

  8. Sumiyoshi T, Meltzer HY. Serotonin 1A receptors in memory function. Am J Psychiatry. 2004;161:1505.

    Article  PubMed  Google Scholar 

  9. Palchaudhuri M, Flugge G. 5-HT1A receptor expression in pyramidal neurons of cortical and limbic brain regions. Cell Tissue Res. 2005;321:159–172.

    Article  PubMed  CAS  Google Scholar 

  10. Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry. 2003;53:193–203.

    Article  PubMed  CAS  Google Scholar 

  11. Blier P, Lista A, De Montigny C. Differential properties of pre-and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins. J Pharmacol Exp Ther. 1993;265:16–23.

    PubMed  CAS  Google Scholar 

  12. Hjorth S, Magnusson T. The 5-HT 1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo. Naunyn Schmiedebergs Arch Pharmacol. 1988;338:463–471.

    Article  PubMed  CAS  Google Scholar 

  13. Hensler JG, Ladenheim EE, Lyons WE. Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice. J Neurochem. 2003;85:1139–1147.

    Article  PubMed  CAS  Google Scholar 

  14. Sharp T, Bramwell SR, Grahame-Smith DG. 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol. 1989;96:283–290.

    PubMed  CAS  Google Scholar 

  15. Kreiss DS, Lucki I. Chronic administration of the 5-HT1A receptor agonist 8-OHDPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei. Synapse. 1997;25:107–116.

    Article  PubMed  CAS  Google Scholar 

  16. Huang YY, Battistuzzi C, Oquendo MA, et al. Human 5-HT1A receptor C(-1019) G polymorphism and psychopathology. Int J Neuropsychopharmacol. 2004;7:441–451.

    Article  PubMed  CAS  Google Scholar 

  17. Reynolds GP, Arranz B, Templeman LA, Fertuzinhos S, San L. Effect of 5-HT1A receptor gene polymorphism on negative and depressive symptom response to antipsychotic treatment of drug-naive psychotic patients. Am J Psychiatry. 2006;163:1826–1829.

    Article  PubMed  Google Scholar 

  18. Hurlemann R, Boy C, Meyer PT, et al. Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia. Anat Embryol (Berl). 2005;210:519–523.

    Article  CAS  Google Scholar 

  19. Unschuld PG, Ising M, Erhardt A, et al. Polymorphisms in the serotonin receptor gene HTR2A are associated with quantitative traits in panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:424–429.

    Article  PubMed  CAS  Google Scholar 

  20. Erdmann J, Shimron-Abarbanell D, Rietschel M, et al. Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet. 1996;97:614–619.

    Article  PubMed  CAS  Google Scholar 

  21. Williams J, Spurlock G, McGuffin P, et al. Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group. Lancet. 1996;347:1294–1296.

    PubMed  CAS  Google Scholar 

  22. Polesskaya OO, Sokolov BP. Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res. 2002;67:812–822.

    Article  PubMed  CAS  Google Scholar 

  23. Arranz M, Collier D, Sodhi M, et al. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet. 1995;346:281–282.

    Article  PubMed  CAS  Google Scholar 

  24. Dubertret C, Hanoun N, Ades J, Hamon M, Gorwood P. Family-based association study of the 5-HT transporter gene and schizophrenia. Int J Neuropsychopharmacol. 2005;8:87–92.

    Article  PubMed  CAS  Google Scholar 

  25. Fan JB, Sklar P. Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Mol Psychiatry. 2005;10:928–938.

    Article  PubMed  CAS  Google Scholar 

  26. Pae CU, Artioli P, Serretti A, et al. No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia. Neurosci Res. 2005;52:195–199.

    Article  PubMed  CAS  Google Scholar 

  27. Chotai J, Serretti A, Lorenzi C. Interaction between the tryptophan hydroxylase gene and the serotonin transporter gene in schizophrenia but not in bipolar or unipolar affective disorders. Neuropsychobiology. 2005;51:3–9.

    Article  PubMed  CAS  Google Scholar 

  28. Pae CU, Kim JJ, Lee SJ, et al. Polymorphism of the serotonin transporter gene and symptomatic dimensions of schizophrenia in the Korean population. Neuropsychobiology. 2003;47:182–186.

    Article  PubMed  CAS  Google Scholar 

  29. Wasserman D, Geijer T, Sokolowski M, et al. Association of the serotonin transporter promotor polymorphism with suicide attempters with a high medical damage. Eur Neuropsychopharmacol. 2007;17:230–233.

    Article  PubMed  CAS  Google Scholar 

  30. Horacek J. The influence of polymorphism for serotonin 5-HT1A receptors on phenotypic variables in schizophrenia. Presented at the 16th European Congress of Psychiatry; April 7, 2008; Nice, France. Symposium: “Role of serotonin-5-HT1A receptors in the pathophysiology and treatment of schizophrenia”.

  31. Buchsbaum MS, Hazlett EA. Functional brain imaging and aging in schizophrenia. Schizophr Res. 1997;27:129–141.

    Article  PubMed  CAS  Google Scholar 

  32. Sumiyoshi T, Higuchi Y, Ito T, et al. Effect of perospirone on P300 electrophysiological activity and social cognition in schizophrenia: a three-dimensional analysis with sLORETA. Psychiatry Res Neuroimaging. In press.

  33. Sumiyoshi T, Higuchi Y, Matsui M, et al. Effective adjunctive use of tandospirone with perospirone for enhancing verbal memory and quality of life in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:965–967.

    Article  PubMed  CAS  Google Scholar 

  34. Sumiyoshi T, Matsui M, Itoh H, et al. Essential polyunsaturated fatty acids and social cognition in schizophrenia. Psychiatry Res. 2008;157:87–93.

    Article  PubMed  CAS  Google Scholar 

  35. Sumiyoshi T, Park S, Jayathilake K, Roy A, Ertugrul A, Meltzer HY. Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2007;95:158–168.

    Article  PubMed  Google Scholar 

  36. Gu Z, Jiang Q, Yan Z. RGS4 modulates serotonin signaling in prefrontal cortex and links to serotonin dysfunction in a rat model of schizophrenia. Mol Pharmacol. 2007;71:1030–1039.

    Article  PubMed  CAS  Google Scholar 

  37. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev. 1999;51:7–61.

    PubMed  CAS  Google Scholar 

  38. Calcagno E, Carli M, Invernizzi RW. The 5-HT1A receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors. J Neurochem. 2006;96:853–860.

    Article  PubMed  CAS  Google Scholar 

  39. Madjid N, Tottie EE, Luttgen M, et al. 5-hydroxytryptamine 1A receptor blockade facilitates aversive learning in mice: interactions with cholinergic and glutamatergic mechanisms. J Pharmacol Exp Ther. 2006;316:581–591.

    Article  PubMed  CAS  Google Scholar 

  40. Bubenikova-Valesova V, Horacek J, Vrajova M, Hoschl C. Models of schizophrenia in humans and animals based on inhibition of NMDA receptors. Neurosci Biobehav Rev. 2008;32:1014–1023.

    Article  PubMed  CAS  Google Scholar 

  41. Andine P, Widermark N, Axelsson R, et al. Characterization of MK-801-induced behavior as a putative rat model of psychosis. J Pharmacol Exp Ther. 1999;290:1393–1408.

    PubMed  CAS  Google Scholar 

  42. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl). 2001;156:117–154.

    Article  CAS  Google Scholar 

  43. Lopez-Gil X, Babot Z, Amargos-Bosch M, Sunol C, Artigas F, Adell A. Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology. 2007;32:2087–2097.

    Article  PubMed  CAS  Google Scholar 

  44. Bubenikova-Valesova V, Votava M, Palenicek T, Horacek J. The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801. Neuropharmacology. 2007;52:1071–1078.

    Article  PubMed  CAS  Google Scholar 

  45. Maj J, Rogoz Z, Skuza G, Wedzony K. The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist. J Neural Transm. 1996;103:131–146.

    Article  PubMed  CAS  Google Scholar 

  46. Dall’Olio R, Gaggi R, Bonfante V, Gandolfi O. The non-competitive NMDA receptor blocker dizocilpine potentiates serotonergic function. Behav Pharmacol. 1999;10:63–71.

    Article  PubMed  CAS  Google Scholar 

  47. Sumiyoshi T, Matsui M, Nohara S, et al. Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry. 2001;158:1722–1725.

    Article  PubMed  CAS  Google Scholar 

  48. Sumiyoshi T, Matsui M, Yamashita I, et al. Effect of adjunctive treatment with serotonin-1A agonist tandospirone on memory functions in schizophrenia. J Clin Psychopharmacol. 2000;20:386–388.

    Article  PubMed  CAS  Google Scholar 

  49. Roth BL, Hanizavareh SM, Blum AE. Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacology (Berl). 2004;174:17–24.

    Article  CAS  Google Scholar 

  50. Bantick RA, Deakin JF, Grasby PM. The 5-HT1A receptor in schizophrenia: a promising target for novel atypical neuroleptics? J Psychopharmacol. 2001;15:37–46.

    Article  PubMed  CAS  Google Scholar 

  51. Sumiyoshi T, Matsui M, Yamashita I, et al. The effect of tandospirone, a serotonin1A agonist, on memory function in schizophrenia. Biol Psychiatry. 2001;49:861–868.

    Article  PubMed  CAS  Google Scholar 

  52. Kusserow H, Davies B, Hortnagl H, et al. Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin1A receptors. Mol Brain Res. 2004;129:104–116.

    Article  PubMed  CAS  Google Scholar 

  53. Bert B, Fink H, Hortnagl H, et al. Mice over-expressing the 5-HT1A receptor in cortex and dentate gyrus display exaggerated locomotor and hypothermic response to 8-OH-DPAT. Behav Brain Res. 2006;167:328–341.

    Article  PubMed  CAS  Google Scholar 

  54. Pazos A, Palacios JM. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res. 1985;346:205–230.

    Article  PubMed  CAS  Google Scholar 

  55. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull. 2000;26:119–136.

    PubMed  CAS  Google Scholar 

  56. Meeter M, Talamini L, Schmitt JA, Riedel WJ. Effects of 5-HT on memory and the hippocampus: model and data. Neuropsychopharmacology. 2006;31:712–720.

    Article  PubMed  CAS  Google Scholar 

  57. Grayson B, Idris NF, Neill JC. Atypical antipsychotics attenuate a sub-chronic PCPinduced cognitive deficit in the novel object recognition task in the rat. Behav Brain Res. 2007;184:31–38.

    Article  PubMed  CAS  Google Scholar 

  58. Bubenikova-Valesova V, Stuchlik A, Svoboda J, Bures J, Vales K. Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task. Proc Natl Acad Sci U S A. 2008;105:1061–1066.

    Article  PubMed  CAS  Google Scholar 

  59. Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F. Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci. 2005;25:10831–10843.

    Article  PubMed  CAS  Google Scholar 

  60. Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY. 5-HT2A and D2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem. 2001;76:1521–1531.

    Article  PubMed  CAS  Google Scholar 

  61. Sato M, Ago Y, Koda K, et al. Role of postsynaptic serotonin1A receptors in risperidone-induced increase in acetylcholine release in rat prefrontal cortex. Eur J Pharmacol. 2007;559:155–160.

    Article  PubMed  CAS  Google Scholar 

  62. Burnet PW, Eastwood SL, Harrison PJ. 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology. 1996;15:442–455.

    Article  PubMed  CAS  Google Scholar 

  63. Burnet PW, Eastwood SL, Harrison PJ. [3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia. Neurochem Int. 1997;30:565–574.

    Article  PubMed  CAS  Google Scholar 

  64. Gurevich EV, Joyce JN. Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biol Psychiatry. 1997;42:529–545.

    Article  PubMed  CAS  Google Scholar 

  65. Hashimoto T, Nishino N, Nakai H, Tanaka C. Increase in serotonin 5HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. Life Sci. 1991;48:355–363.

    Article  PubMed  CAS  Google Scholar 

  66. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE. Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology. 1993;8:315–336.

    PubMed  CAS  Google Scholar 

  67. Simpson MDC, Lubman DI, Slater P, Deakin JFW. Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT1A receptors in ventral prefrontal cortex in schizophrenia. Biol Psychiatry. 1996;39:919–928.

    Article  PubMed  CAS  Google Scholar 

  68. Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY. Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res. 1996;708:209–214.

    Article  PubMed  CAS  Google Scholar 

  69. Kasper S, Tauscher J, Willeit M, et al. Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette’s disorder-implications for psychopharmacology. World J Biol Psychiatry. 2002;3:133–146.

    Article  PubMed  Google Scholar 

  70. Tauscher J, Meyer JH, Smith GS, Rabiner EA. Imaging of the serotonin system in depression and schizophrenia. Biol Psychiatry. 2002;51:146S.

    Google Scholar 

  71. Hamik A, Oksenberg D, Fischette C, Peroutka SJ. Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites. Biol Psychiatry. 1990;28:99–109.

    Article  PubMed  CAS  Google Scholar 

  72. Miller LG, Thompson ML, Byrnes JJ, Greenblatt DJ, Shemer A. Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine. J Clin Psychopharmacol. 1992;12:341–345.

    PubMed  CAS  Google Scholar 

  73. Sumiyoshi C, Sumiyoshi T, Roy A, Jayathilake K, Meltzer HY. Atypical antipsychotic drugs and organization of long-term semantic memory: multidimensional scaling and cluster analyses of category fluency performance in schizophrenia. Int J Neuropsychopharmacol. 2006;9:677–683.

    Article  PubMed  CAS  Google Scholar 

  74. Araki T, Yamasue H, Sumiyoshi T, et al. Perospirone in the treatment of schizophrenia: effect on verbal memory organization. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:204–208.

    Article  PubMed  CAS  Google Scholar 

  75. Keefe RS, Bilder RM, Harvey PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology. 2006;31:2033–2046.

    Article  PubMed  Google Scholar 

  76. Cosi C, Waget A, Rollet K, Tesori V, Newman-Tancredi A. Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation. Brain Res. 2005;1043:32–41.

    Article  PubMed  CAS  Google Scholar 

  77. Uehara T, Sumiyoshi T, Matsuoka T, Itoh H, Kurachi M. Role of 5-HT1A receptors in the modulation of stressinduced lactate metabolism in the medial prefrontal cortex and basolateral amygdala. Psychopharmacology (Berl). 2006;186:218–225.

    Article  CAS  Google Scholar 

  78. Hagiwara H, Fujita Y, Ishima T, et al. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone: role of serotonin 5-HT1A receptors. Eur Neuropsychopharmacol. 2008;18:448–454.

    Article  PubMed  CAS  Google Scholar 

  79. Luttgen M, Ogren SO, Meister B. 5-HT1A receptor mRNA and immunoreactivity in the rat medial septum/diagonal band of Broca-relationships to GABAergic and cholinergic neurons. J Chem Neuroanat. 2005;29:93–111.

    Article  PubMed  CAS  Google Scholar 

  80. Schiapparelli L, Simon AM, Del Rio J, Frechilla D. Opposing effects of AMPA and 5-HT1A receptor blockade on passive avoidance and object recognition performance: correlation with AMPA receptor subunit expression in rat hippocampus. Neuropharmacology. 2006;50:897–907.

    Article  PubMed  CAS  Google Scholar 

  81. Boulay D, Depoortere R, Louis C, Perrault G, Griebel G, Soubrie P. SSR181507, a putative atypical antipsychotic with dopamine D2 antagonist and 5-HT1A agonist activities: improvement of social interaction deficits induced by phencyclidine in rats. Neuropharmacology. 2004;46:1121–1129.

    Article  PubMed  CAS  Google Scholar 

  82. Depoortere R, Bardin L, Auclair AL, et al. F15063, a compound with D2/D3 antagonist, 5-HT1A agonist and D4 partial agonist properties. II. Activity in models of positive symptoms of schizophrenia. Br J Pharmacol. 2007;151:253–265.

    Article  PubMed  CAS  Google Scholar 

  83. McCreary AC, Glennon JC, Ashby CR Jr, et al. SLV313 (1-(2,3-dihydrobenzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine monohydrochloride): a novel dopamine D2 receptor antagonist and 5-HT1A receptor agonist potential antipsychotic drug. Neuropsychopharmacology. 2007;32:78–94.

    Article  PubMed  CAS  Google Scholar 

  84. Newman-Tancredi A, Cussac D, Depoortere R. Neuropharmacological profile of bifeprunox: merits and limitations in comparison with other third-generation antipsychotics. Curr Opin Investig Drugs. 2007;8:539–554.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan

    Tomiki Sumiyoshi

  2. Prague Psychiatric Center and Center of Neuropsychiatry Studies, Prague, Czech Republic

    Vera Bubenikova-Valesova & Jiri Horacek

  3. Institute of Pharmacology and Toxicology, School for Veterinary Medicine, Freie University, Berlin, Germany

    Bettina Bert

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  1. Tomiki Sumiyoshi
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  2. Vera Bubenikova-Valesova
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  3. Jiri Horacek
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  4. Bettina Bert
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Sumiyoshi, T., Bubenikova-Valesova, V., Horacek, J. et al. Serotonin1A receptors in the pathophysiology of schizophrenia: development of novel cognition-enhancing therapeutics. Adv Therapy 25, 1037–1056 (2008). https://doi.org/10.1007/s12325-008-0102-2

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