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Antipsychotics/Neuroleptics: Pharmacology and Biochemistry

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Abstract

Antipsychotics are a group of drugs used to treat schizophrenia, some of which are also used to treat mood disorders and anxiety disorders. Antipsychotic drugs are sometimes referred to as neuroleptic drugs due to the neuroleptic effect of early antipsychotics. These drugs are roughly classified into first-generation antipsychotics (FGA) based on their dopamine D2 receptor-blocking action and second-generation antipsychotics (SGA) represented by a serotonin-dopamine antagonist (SDA). There is no significant difference in the therapeutic effect among antipsychotics, but side effects differ between drugs. The development of antipsychotics began with the serendipitous discovery of chlorpromazine in the 1950s and was dominated by phenothiazines and butyrophenones, which act as dopamine D2 receptor blockers, based on the dopamine hypothesis of the pathogenesis of schizophrenia. However, because FGA present challenges such as drug-induced extrapyramidal symptoms, hyperprolactinemia, and worsening negative symptoms, SGA focusing on actions other than D2 receptors have become the mainstay of treatment since the 1990s. In this chapter, the pharmacological action and biochemical function of antipsychotic drugs are explained.

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References

  • Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332(7539):455–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Araki T, Yamasue H, Sumiyoshi T, Kuwabara H, Suga M, Iwanami A, Kato N, Kasai K. Perospirone in the treatment of schizophrenia: effect on verbal memory organization. Prog Neuro-Psychopharmacol Biol Psychiatry. 2006;30(2):204–8.

    Article  CAS  Google Scholar 

  • Ben-Jonathan N, Hnasko R. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev. 2001;22(6):724–63.

    Article  CAS  PubMed  Google Scholar 

  • Björklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci. 2007;30(5):194–202.

    Article  PubMed  Google Scholar 

  • Bymaster FP, Rasmussen K, Calligaro DO, Nelson DL, DeLapp NW, Wong DT, Moore NA. In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug. J Clin Psychiatry. 1997;58(Suppl 10):28–36.

    CAS  PubMed  Google Scholar 

  • Corena-McLeod M. Comparative pharmacology of risperidone and paliperidone. Drugs R D. 2015;15(2):163–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Creese I, Burt DR, Snyder SH. Dopamine receptors and average clinical doses. Science. 1976;194(4264):546.

    Article  CAS  PubMed  Google Scholar 

  • Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991;148(11):1474–86.

    Article  CAS  PubMed  Google Scholar 

  • Deeks ED, Keating GM. Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010;24(1):65–84.

    Article  CAS  PubMed  Google Scholar 

  • Granger B, Albu S. The haloperidol story. Ann Clin Psychiatry. 2005;17(3):137–40.

    Article  PubMed  Google Scholar 

  • Gross G, Wicke K, Drescher KU. Dopamine D3 receptor antagonism--still a therapeutic option for the treatment of schizophrenia. Naunyn Schmiedeberg’s Arch Pharmacol. 2013;386(2):155–66.

    Article  CAS  Google Scholar 

  • Hamamura T, Harada T. Unique pharmacological profile of aripiprazole as the phasic component buster. Psychopharmacology (Berl). 2007;191(3):741–3.

    Article  CAS  Google Scholar 

  • Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine’s antidepressant activity. Neuropsychopharmacology. 2008;33(10):2303–12.

    Article  CAS  PubMed  Google Scholar 

  • Joyce EM, Roiser JP. Cognitive heterogeneity in schizophrenia. Curr Opin Psychiatry. 2007;20(3):268–72.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kapur S, Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry. 1996;153(4):466–76.

    Article  CAS  PubMed  Google Scholar 

  • Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry. 2001;158(3):360–9.

    Article  CAS  PubMed  Google Scholar 

  • Keks N, Hope J, Schwartz D, McLennan H, Copolov D, Meadows G. Comparative tolerability of dopamine D2/3 receptor partial agonists for schizophrenia. CNS Drugs. 2020;34(5):473–507.

    Article  CAS  PubMed  Google Scholar 

  • Kornhuber J, Riederer P, Reynolds GP, Beckmann H, Jellinger K, Gabriel E. 3H-spiperone binding sites in post-mortem brains from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms. J Neural Transm. 1989;75(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  • Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2003;28(3):519–26.

    Article  CAS  PubMed  Google Scholar 

  • Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373(9657):31–41.

    Article  CAS  PubMed  Google Scholar 

  • Lieberman JA, Mailman R, Duncan G, Sikich L, Chakos M, Nichols DE, Kraus JE. Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry. 1998;44(11):1099–117.

    Article  CAS  PubMed  Google Scholar 

  • Mauri MC, Bravin S, Bitetto A, Rudelli R, Invernizzi G. A risk-benefit assessment of sulpiride in the treatment of schizophrenia. Drug Saf. 1996;14(5):288–98.

    Article  CAS  PubMed  Google Scholar 

  • Meftah AM, Deckler E, Citrome L, Kantrowitz JT. New discoveries for an old drug: a review of recent olanzapine research. Postgrad Med. 2020;132(1):80–90.

    Article  PubMed  Google Scholar 

  • Meltzer HY. Clozapine: balancing safety with superior antipsychotic efficacy. Clin Schizophr Relat Psychoses. 2012;6(3):134–44.

    Article  PubMed  Google Scholar 

  • Michael JO, Akira S, Mortensen PB. Schizophrenia. Lancet. 2016;388(10039):86–97.

    Article  Google Scholar 

  • Nicola SM, Surmeier J, Malenka RC. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci. 2000;23(2):185–215.

    Article  CAS  PubMed  Google Scholar 

  • Nucifora FC Jr, Mihaljevic M, Lee BJ, Sawa A. Clozapine as a model for antipsychotic development. Neurotherapeutics. 2017;14(3):750–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohlow MJ, Moosmann B. Phenothiazine: the seven lives of pharmacology’s first lead structure. Drug Discov Today. 2011;16(3–4):119–31.

    Article  CAS  PubMed  Google Scholar 

  • Pytliak M, Vargová V, Mechírová V, Felšöci M. Serotonin receptors – from molecular biology to clinical applications. Physiol Res. 2011;60(1):15–25.

    Article  CAS  PubMed  Google Scholar 

  • Remington G. Alterations of dopamine and serotonin transmission in schizophrenia. Prog Brain Res. 2008;172:117–40.

    Article  CAS  PubMed  Google Scholar 

  • Reyad AA, Mishriky R. Asenapine: pharmacological aspects and role in psychiatric disorders. Psychiatr Danub. 2019;31(2):157–61.

    Article  CAS  PubMed  Google Scholar 

  • Robert AM, Anissa AD, Oliver DH. Schizophrenia, dopamine and the striatum: from biology to symptoms. Trends Neurosci. 2019;42(3):205–20.

    Article  Google Scholar 

  • Seeman P, Tallerico T. Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry. 1998;3(2):123–34.

    Article  CAS  PubMed  Google Scholar 

  • Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature. 1976;261(5562):717–9.

    Article  CAS  PubMed  Google Scholar 

  • Seeman P, Ulpian C, Bergeron C, Riederer P, Jellinger K, Gabriel E, Reynolds GP, Tourtellotte WW. Bimodal distribution of dopamine receptor densities in brains of schizophrenics. Science. 1984;225(4663):728–31.

    Article  CAS  PubMed  Google Scholar 

  • Stahl SM. Mechanism of action of brexpiprazole: comparison with aripiprazole. CNS Spectr. 2016;21(1):1–6.

    Article  PubMed  Google Scholar 

  • van Rossum JM. The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs. Arch Int Pharmacodyn Ther. 1966;160(2):492–4.

    PubMed  Google Scholar 

  • Waugh DJ, Gaivin RJ, Damron DS, Murray PA, Perez DM. Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: a potential site of allosteric modulation. J Pharmacol Exp Ther. 1999;291(3):1164–71.

    CAS  PubMed  Google Scholar 

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Correspondence to Hiroki Ozawa .

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Yonezawa, K., Kanegae, S., Ozawa, H. (2021). Antipsychotics/Neuroleptics: Pharmacology and Biochemistry. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_52-1

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  • DOI: https://doi.org/10.1007/978-3-319-56015-1_52-1

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  • Print ISBN: 978-3-319-56015-1

  • Online ISBN: 978-3-319-56015-1

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