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  • 1 Vas Megyei Markusovszky Kórház Nonprofit Zrt. Pszichiátriai Centrum Szombathely 11-es Huszár út 138. 9700
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Az atípusos (második generációs) antipszichotikumok forradalmi változást hoztak a szkizofrénia és az egyéb pszichotikus zavarok farmakoterápiájában. A jelenleg alkalmazott atípusos szerek fő jellemzője a viszonylag gyenge D 2 -receptor-gátlás, jóval erősebb szerotonin-5-HT 2A -blokkolás mellett. Ezen jellemzők tehetők részben felelőssé a második generációs szerek hatékonyságáért a negatív, a kognitív és az affektív tünetek területén, amely a konvencionális antipszichotikumokra nem vagy csak alig jellemző. A második generációs szerek közül több molekulánál jellemző a D 2 -receptorról történő gyors disszociáció, amely szintén az atípusos hatásmechanizmus egyik fontos részjelensége lehet. A többféle jeltovábbító rendszer befolyásolása révén az atípusos antipszichotikumok konvencionális társaiknál jóval nagyobb szereppel bírnak a neuronalis plaszticitás megőrzésében. A multiplex neurobiológiai hatásmechanizmus révén a második generációs szerek neuroprotektív mechanizmusaik révén a szkizofrénia kezelésében új minőséget jelentenek.

  • Pierre, J. M.: Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf., 2005, 28 , 191–208.

    Pierre J. M. , 'Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management ' (2005 ) 28 Drug Saf. : 191 -208.

    • Search Google Scholar
  • Conley, R. R., Kelly, D. L.: Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects. Isr. J. Psychiatry Relat. Sci., 2005, 42 , 51–60.

    Kelly D. L. , 'Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects ' (2005 ) 42 Isr. J. Psychiatry Relat. Sci. : 51 -60.

    • Search Google Scholar
  • Kane, J. M., Carson, W. H., Saha, A. R. és mtsai: Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J. Clin. Psychiatry, 2002, 63 , 763–771.

    Saha A. R. , 'Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder ' (2002 ) 63 J. Clin. Psychiatry : 763 -771.

    • Search Google Scholar
  • Kasper, S., Lerman, M. N., McQuade, R. D. és mtsai: Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int. J. Neuropsychopharmacol., 2003, 6 , 325–337.

    McQuade R. D. , 'Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia ' (2003 ) 6 Int. J. Neuropsychopharmacol. : 325 -337.

    • Search Google Scholar
  • Hirsch, S. R., Kissling, W., Bauml, J. és mtsai: A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J. Clin. Psychiatry, 2002, 63 , 516–523.

    Bauml J. , 'A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia ' (2002 ) 63 J. Clin. Psychiatry : 516 -523.

    • Search Google Scholar
  • Marder, S. R., Glynn, S. M., Wirshing, W. C. és mtsai: Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. Am. J Psychiatry, 2003, 160 , 1405–1412.

    Wirshing W. C. , 'Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes ' (2003 ) 160 Am. J Psychiatry : 1405 -1412.

    • Search Google Scholar
  • Tollefson, G., Beasley, C., Tran, P. és mtsai: Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am. J. Psychiatry, 1997, 154 , 457–465.

    Tran P. , 'Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial ' (1997 ) 154 Am. J. Psychiatry : 457 -465.

    • Search Google Scholar
  • Glick, I., Davis, J., Chen, N.: A meta-analysis of the efficacy of second generation antipsychotics. Schizophr. Res., 2003, 60 , 285.

    Chen N. , 'A meta-analysis of the efficacy of second generation antipsychotics ' (2003 ) 60 Schizophr. Res. : 285 -.

    • Search Google Scholar
  • Grace, A. A.: Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience, 1991, 41 , 1–24.

    Grace A. A. , 'Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia ' (1991 ) 41 Neuroscience : 1 -24.

    • Search Google Scholar
  • Horvitz, J. C., Stewart, T., Jacobs, B. L.: Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat. Brain Res., 1997, 759 , 251–258.

    Jacobs B. L. , 'Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat ' (1997 ) 759 Brain Res. : 251 -258.

    • Search Google Scholar
  • Lieberman, J. A. és mtsai: Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch. Gen. Psychiatry., 2005, 62 , 361–370.

    Lieberman J. A. , 'Antipsychotic drug effects on brain morphology in first-episode psychosis ' (2005 ) 62 Arch. Gen. Psychiatry. : 361 -370.

    • Search Google Scholar
  • Lieberman, J. A. és mtsai: Antipsychotic drugs: Comparison in animal models of efficacy, neurotransmitter regulation and neuroprotection. Pharm. Rev., 2008, 60 , 358–403.

    Lieberman J. A. , 'Antipsychotic drugs: Comparison in animal models of efficacy, neurotransmitter regulation and neuroprotection ' (2008 ) 60 Pharm. Rev. : 358 -403.

    • Search Google Scholar
  • Seeman, P., Tallerico, T.: Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am. J. Psychiatry, 1999, 156 , 876–884.

    Tallerico T. , 'Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine ' (1999 ) 156 Am. J. Psychiatry : 876 -884.

    • Search Google Scholar
  • Strange, P. G.: Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol. Rev., 2001, 53 , 119–133.

    Strange P. G. , 'Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects ' (2001 ) 53 Pharmacol. Rev. : 119 -133.

    • Search Google Scholar
  • Kapur, S., Seeman, P.: Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J. Psychiatry Neurosci., 2000, 25 , 161–166.

    Seeman P. , 'Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action ' (2000 ) 25 J. Psychiatry Neurosci. : 161 -166.

    • Search Google Scholar
  • Kapur, S., Zipursky, R., Jones, C. és mtsai: Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am. J. Psychiatry, 2000, 157 , 514–520.

    Jones C. , 'Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia ' (2000 ) 157 Am. J. Psychiatry : 514 -520.

    • Search Google Scholar
  • Kapur, S., Zipursky, R., Jones, C. és mtsai: A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch. Gen. Psychiatry, 2000, 57 , 553.

    Jones C. , 'A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy ' (2000 ) 57 Arch. Gen. Psychiatry : 553 -.

    • Search Google Scholar
  • Jakab, R., Goldman-Rakic, P.: 5-hydroxytryptamine 2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc. Natl. Acad. Sci. USA, 1998, 95 , 735–740.

    Goldman-Rakic P. , '5-hydroxytryptamine 2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites ' (1998 ) 95 Proc. Natl. Acad. Sci. USA : 735 -740.

    • Search Google Scholar
  • Miner, L. A. H., Backstrom, J. R., Sanders-Bush, E. és mtsa: Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex. Neuroscience, 2003, 116 , 107–117.

    Sanders-Bush E. , 'Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex ' (2003 ) 116 Neuroscience : 107 -117.

    • Search Google Scholar
  • Rolls, E. T., Loh, M., Deco, G. és mtsa: Computational models of schizophrenia and dopamine modulation in the prefrontal cortex. Nature Reviews Neuroscience, 2008, 9 , 696–709.

    Deco G. , 'Computational models of schizophrenia and dopamine modulation in the prefrontal cortex ' (2008 ) 9 Nature Reviews Neuroscience : 696 -709.

    • Search Google Scholar
  • Meltzer, H. Y.: What’s atypical about atypical antipsychotic drugs? Current Opinion in Pharmacology, 2004, 4 , 53–57.

    Meltzer H. Y. , 'What’s atypical about atypical antipsychotic drugs? ' (2004 ) 4 Current Opinion in Pharmacology : 53 -57.

    • Search Google Scholar
  • Greengard, P.: The neurobiology of slow synaptic transmission. Science, 2001, 294 , 1024–1030.

    Greengard P. , 'The neurobiology of slow synaptic transmission ' (2001 ) 294 Science : 1024 -1030.

    • Search Google Scholar
  • Missale, C., Nash, S. R., Robinson, S. W. és mtsai: Dopamine receptors: from structure to function. Physiol. Rev., 1998, 78 , 189–225.

    Robinson S. W. , 'Dopamine receptors: from structure to function ' (1998 ) 78 Physiol. Rev. : 189 -225.

    • Search Google Scholar
  • Beaulieu, J. M. és mtsai: An Akt/b-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell, 2005, 122 , 261–273.

    Beaulieu J. M. , 'An Akt/b-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior ' (2005 ) 122 Cell : 261 -273.

    • Search Google Scholar
  • Shenoy, S. K., Lefkowitz, R. J.: Multifaceted roles of b arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling. Biochem. J., 2003, 375 , 503–515.

    Lefkowitz R. J. , 'Multifaceted roles of b arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling ' (2003 ) 375 Biochem. J. : 503 -515.

    • Search Google Scholar
  • Luttrell, L. M., Roudabush, F. L., Choy, E. W. és mtsai: Activation and targeting of extracellular signal-regulated kinases by b-arrestin scaffolds. Proc. Natl. Acad. Sci. USA, 2001, 98 , 2449–2454.

    Choy E. W. , 'Activation and targeting of extracellular signal-regulated kinases by b-arrestin scaffolds ' (2001 ) 98 Proc. Natl. Acad. Sci. USA : 2449 -2454.

    • Search Google Scholar
  • Beaulieu, J. M., Sotnikova, T. D., Gainetdinov, R. R. és mtsa: Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. J. Biol. Chem., 2006, 281 , 32072–32080.

    Gainetdinov R. R. , 'Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice ' (2006 ) 281 J. Biol. Chem. : 32072 -32080.

    • Search Google Scholar
  • Beaulieu, J. M., Sotnikova, T. D., Yao, W. D. és mtsai: Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc. Natl. Acad. Sci. USA, 2004, 101 , 5099–5104.

    Yao W. D. , 'Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade ' (2004 ) 101 Proc. Natl. Acad. Sci. USA : 5099 -5104.

    • Search Google Scholar
  • Frame, S., Cohen, P.: GSK3 takes centre stage more than 20 years after its discovery. Biochem. J., 2001, 359 , 1–16.

    Cohen P. , 'GSK3 takes centre stage more than 20 years after its discovery ' (2001 ) 359 Biochem. J. : 1 -16.

    • Search Google Scholar
  • Jarskog, L. F., Selinger, E. S., Lieberman, J. A. és mtsa: Apoptotic proteins in the temporal cortex in schizophrenia: High Bax/Bcl-2 ratio without caspase-3 activation. Am. J. Psychiatry, 2004, 161 , 109–115.

    Lieberman J. A. , 'Apoptotic proteins in the temporal cortex in schizophrenia: High Bax/Bcl-2 ratio without caspase-3 activation ' (2004 ) 161 Am. J. Psychiatry : 109 -115.

    • Search Google Scholar
  • Pap, M., Cooper, G. M.: Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway. J. Biol. Chem., 1998, 273 , 19929–19932.

    Cooper G. M. , 'Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway ' (1998 ) 273 J. Biol. Chem. : 19929 -19932.

    • Search Google Scholar
  • Kaytor, M. D., Orr, H. T.: The GSK3 beta signaling cascade and neurodegenerative disease. Curr. Opin. Neurobiol., 2002, 12 , 275–278.

    Orr H. T. , 'The GSK3 beta signaling cascade and neurodegenerative disease ' (2002 ) 12 Curr. Opin. Neurobiol. : 275 -278.

    • Search Google Scholar
  • Beurel, E., Jope, R. S.: The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog. Neurobiol., 2006, 79 , 173–189.

    Jope R. S. , 'The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways ' (2006 ) 79 Prog. Neurobiol. : 173 -189.

    • Search Google Scholar
  • Kang, U. G., Seo, M. S., Roh, M. S. és mtsai: The effects of clozapine on the GSK-3-mediated signaling pathway. FEBS Lett., 2004, 560 , 115–119.

    Roh M. S. , 'The effects of clozapine on the GSK-3-mediated signaling pathway ' (2004 ) 560 FEBS Lett. : 115 -119.

    • Search Google Scholar
  • Li, X., Rosborough, K. M., Friedman, A. B. és mtsai: Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. International Journal of Neuropsychopharmacology, 2007, 10 , 7–17.

    Friedman A. B. , 'Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics ' (2007 ) 10 International Journal of Neuropsychopharmacology : 7 -17.

    • Search Google Scholar
  • Li, X., Zhu, W., Roh, M. S. és mtsai: In vivo regulation of glycogen synthase kinase-3b (GSK3b) by serotonergic activity in mouse brain. Neuropsychopharmacology, 2004, 29 , 1426–1431.

    Roh M. S. , 'In vivo regulation of glycogen synthase kinase-3b (GSK3b) by serotonergic activity in mouse brain ' (2004 ) 29 Neuropsychopharmacology : 1426 -1431.

    • Search Google Scholar