cmedasНепрерывное медицинское образование и наукаContinuing Medical Education and Science2949-62923033-585XAGUcmedas-98Research ArticleЛИТЕРАТУРНЫЙ ОБЗОРLITERARY REVIEWНовые возможности терапии больных с психическими расстройствами (литературный обзор)New treatment options for patients with mental disorders (literature review)СемёноваЕ. М.SemyonovaE. M.

Семенова Екатерина Михайловна, студентка 5-го  курса лечебного факультета

454092, г.   Челябинск , ул. Воровского, 64; тел. +7 351 232-73-69

Chelyabinsk

ekaterina.sem1197@mail.ruМалининаЕ. В.MalininaE. V.

Малинина Елена Викторовна, доктор медицинских наук,  профессор, заведующая кафедрой психиатрии

Челябинск

Chelyabinsk

malinina.e@rambler.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Южно-Уральский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияSouth-Urals State Medical UniversityRussian Federation2020050820231523139Copyright © Семёнова Е.М., Малинина Е.В., 20232023Семёнова Е.М., Малинина Е.В.Semyonova E.M., Malinina E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cmedas.elpub.ru/jour/article/view/98

В данной работе представлен обзор нового препарата карипразин, в частности, отображена его фармакодинамика (выступает в качестве парциального агониста D2- и D3-дофаминовых рецепторов, агониста 5-HT1А-серотониновых рецепторов, антагониста 5-НТ2В-, 5-НТ2Аи 5-НТ2С-серотониновых рецепторов), которая принципиально отличает новый нейролептик от предшественников; фармакокинетика, согласно которой карипразин обладает самым длительным среди представленных сегодня на рынке пероральных антипсихотиков периодом полувыведения (от 2 до 6 суток); рассмотрены клинические исследования, их результаты и побочные действия нового препарата как самостоятельно, так и в сравнении с другими антипсихотическими препаратами.

This work provides an overview of the new drug cariprazine in particular, its pharmacodynamics (acts as a partial agonist of D2- and D3-dopamine receptors, agonist of 5-HT1A-serotonin receptors, antagonist of 5-HT2B-, 5-HT2A- and 5-HT2C-serotonin receptors), which fundamentally distinguishes the new drug from its predecessors; according to the pharmacokinetics, cariprazine has the longest half-life of 2 to 6 days among the oral antipsychotics on the market today; clinical trials, their results and side effects of the new drug, both independently and in comparison with other antipsychotic drugs, are considered.

шизофрениябиполярное аффективное расстройствокарипразиндофаминовые рецепторыschizophreniabipolar affective disordercariprazinedopamine receptorsReferencesБыков Ю. В., Беккер Р. А., Морозов П. В. Эффективность карипразина в лечении шизофрении, особенно с преобладанием негативной симптоматики // Психиатрия и психофармакотерапия. 2018. № 5. С. 27–37.Быков Ю. В., Беккер Р. А., Морозов П. В. Эффективность карипразина в лечении шизофрении, особенно с преобладанием негативной симптоматики // Психиатрия и психофармакотерапия. 2018. № 5. С. 27–37.Морозов П. В., Медведев В. Э. Карипразин — новый антипсихотик для лечения эндогенных психических расстройств // Психиатрия и психофармакотерапия. 2014. Т. 16, № 1. С. 9–14.Морозов П. В., Медведев В. Э. Карипразин — новый антипсихотик для лечения эндогенных психических расстройств // Психиатрия и психофармакотерапия. 2014. Т. 16, № 1. С. 9–14.Шмуклер А. Б. Карипразин — антипсихотик с новыми уникальными потенциальными возможностями для лечения шизофрении и аффективных расстройств // Социальная и клиническая психиатрия. 2014. Т. 24, № 2. С. 72–75.Шмуклер А. Б. Карипразин — антипсихотик с новыми уникальными потенциальными возможностями для лечения шизофрении и аффективных расстройств // Социальная и клиническая психиатрия. 2014. Т. 24, № 2. С. 72–75.Caccia S., Invernizzi R. W., Nobili A. et al. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia // Therapeutics and Clinical Risk Management. 2013. Vol. 9. P. 319–328.Caccia S., Invernizzi R. W., Nobili A. et al. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia // Therapeutics and Clinical Risk Management. 2013. Vol. 9. P. 319–328.Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.Calabrese J. R., Keck P. E. Jr., Starace A. et al. Efficacy and safety of low-and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study // The Journal of Clinical Psychiatry. 2014. Vol. 76, № 3. P. 284–292.Choi Y. K., Adham N., Kiss B. et al. Long-term effects of cariprazine exposure on dopamine receptor subtypes // CNS Spectrums. 2014. Vol. 19, № 3. P. 268–277.Choi Y. K., Adham N., Kiss B. et al. Long-term effects of cariprazine exposure on dopamine receptor subtypes // CNS Spectrums. 2014. Vol. 19, № 3. P. 268–277.Citrome L., Durgam S., Lu K. et al. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials // The Journal of Clinical Psychiatry. 2016. Vol. 77, № 1. P. 109–115.Citrome L., Durgam S., Lu K. et al. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials // The Journal of Clinical Psychiatry. 2016. Vol. 77, № 1. P. 109–115.Citrome L. Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability // Expert Opinion on Drug Metabolism & Toxicology. 2013. Vol. 9, № 2. P. 193–206.Citrome L. Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability // Expert Opinion on Drug Metabolism & Toxicology. 2013. Vol. 9, № 2. P. 193–206.Citrome L. Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy // Advances in Therapy. 2013. Vol. 30, № 2. С. 102–113.Citrome L. Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy // Advances in Therapy. 2013. Vol. 30, № 2. С. 102–113.Cutler A. J., Durgam S., Wang Y. et al. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study // CNS Spectrums. 2018. Vol. 23, № 1. P. 39–50.Cutler A. J., Durgam S., Wang Y. et al. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study // CNS Spectrums. 2018. Vol. 23, № 1. P. 39–50.De P. D. Cariprazine: New dopamine biased agonist for neuropsychiatric disorders // Drugs of Today (Barcelona, Spain: 1998). 2016. Vol. 52, № 2. P. 97–110.De P. D. Cariprazine: New dopamine biased agonist for neuropsychiatric disorders // Drugs of Today (Barcelona, Spain: 1998). 2016. Vol. 52, № 2. P. 97–110.Durgam S., Cutler A. J., Lu K. et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo-and active-controlled trial // The Journal of Clinical Psychiatry. 2015. Vol. 76, № 12. P. e1574–e1582.Durgam S., Cutler A. J., Lu K. et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo-and active-controlled trial // The Journal of Clinical Psychiatry. 2015. Vol. 76, № 12. P. e1574–e1582.Durgam S., Earley W., Li R. et al. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial // Schizophrenia Research. 2016. Vol. 176, № 2–3. P. 264–271.Durgam S., Earley W., Li R. et al. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial // Schizophrenia Research. 2016. Vol. 176, № 2–3. P. 264–271.Durgam S., Greenberg W. M., Li D. et al. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study // Psychopharmacology. 2017. Vol. 234, № 2. P. 199–209.Durgam S., Greenberg W. M., Li D. et al. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study // Psychopharmacology. 2017. Vol. 234, № 2. P. 199–209.Durgam S., Starace A., Li D. et al. An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial // Schizophrenia Research. 2014. Vol. 152, № 2–3. P. 450–457.Durgam S., Starace A., Li D. et al. An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial // Schizophrenia Research. 2014. Vol. 152, № 2–3. P. 450–457.Earley W., Durgam S., Lu K. et al. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies // International Clinical Psychopharmacology. 2017. Vol. 32, № 6. P. 319–328.Earley W., Durgam S., Lu K. et al. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies // International Clinical Psychopharmacology. 2017. Vol. 32, № 6. P. 319–328.Gyertyán I., Kiss B., Sághy K. et al. Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents // Neurochemistry International. 2011. Vol. 59, № 6. P. 925–935.Gyertyán I., Kiss B., Sághy K. et al. Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents // Neurochemistry International. 2011. Vol. 59, № 6. P. 925–935.Joyce J. N., Millan M. J. Dopamine D3 receptor antagonists as therapeutic agents // Drug Discovery Today. 2005. Vol. 10, № 13. P. 917–925.Joyce J. N., Millan M. J. Dopamine D3 receptor antagonists as therapeutic agents // Drug Discovery Today. 2005. Vol. 10, № 13. P. 917–925.Kane J. M., Zukin S., Wang Y. et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial // Journal of Clinical Psychopharmacology. 2015. Vol. 35, № 4. P. 367–373.Kane J. M., Zukin S., Wang Y. et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial // Journal of Clinical Psychopharmacology. 2015. Vol. 35, № 4. P. 367–373.Kapás M., Pásztor Mészáros G., Yu B. et al. P.3.c.051 Comparison of the pharmacokinetic behaviour of RGH-188 in schizophrenic patients and healthy volunteers // European Neuropsychopharmacology. 2008. Vol. 18, suppl. 4. P. S433.Kapás M., Pásztor Mészáros G., Yu B. et al. P.3.c.051 Comparison of the pharmacokinetic behaviour of RGH-188 in schizophrenic patients and healthy volunteers // European Neuropsychopharmacology. 2008. Vol. 18, suppl. 4. P. S433.Keck P. E., Zukin S., Lu K. Efficacy of cariprazine on YMRS single items: a pooled analysis of 3 randomized double-blind, placebo-controlled trials in bipolar mania // Proceedings of the 29th CINP World College of Neuropsychopharmacology, Vancouver, British Columbia, Canada. 2014.Keck P. E., Zukin S., Lu K. Efficacy of cariprazine on YMRS single items: a pooled analysis of 3 randomized double-blind, placebo-controlled trials in bipolar mania // Proceedings of the 29th CINP World College of Neuropsychopharmacology, Vancouver, British Columbia, Canada. 2014.Kiss B., Horváth A., Némethy Z. et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile // Journal of Pharmacology and Experimental Therapeutics. 2010. Vol. 333, № 1. P. 328–340.Kiss B., Horváth A., Némethy Z. et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile // Journal of Pharmacology and Experimental Therapeutics. 2010. Vol. 333, № 1. P. 328–340.Kiss B., Laszlovszky I., Horváth A. et al. Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15 // Naunyn-Schmiedeberg's Archives of Pharmacology. 2008. Vol. 378, № 5. P. 515–528.Kiss B., Laszlovszky I., Horváth A. et al. Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15 // Naunyn-Schmiedeberg's Archives of Pharmacology. 2008. Vol. 378, № 5. P. 515–528.Laszlovsky I. et al. Dopamine D2/D3 receptor occupancy of RGH-188, a D3/D2 antagonist/partial agonist antipsychotic, in healthy volunteers // European Neuropsychopharmacology. 2007. Vol. 17 (Suppl. 4). P. 455.Laszlovsky I. et al. Dopamine D2/D3 receptor occupancy of RGH-188, a D3/D2 antagonist/partial agonist antipsychotic, in healthy volunteers // European Neuropsychopharmacology. 2007. Vol. 17 (Suppl. 4). P. 455.Mészáros G. P. et al. Pharmacokinetics of RGH-188, a new dopamine D3/D2 antagonist/partial agonist atypical antipsychotic, in healthy subjects // European Neuropsychopharmacology. 2007. № 17. P. S451–S452.Mészáros G. P. et al. Pharmacokinetics of RGH-188, a new dopamine D3/D2 antagonist/partial agonist atypical antipsychotic, in healthy subjects // European Neuropsychopharmacology. 2007. № 17. P. S451–S452.Nasrallah H. A., Earley W., Cutler A. J. et al. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis // BMC Psychiatry. 2017. Vol. 17, № 1. P. 305.Nasrallah H. A., Earley W., Cutler A. J. et al. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis // BMC Psychiatry. 2017. Vol. 17, № 1. P. 305.Németh G., Laszlovszky I., Czobor P. et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial // The Lancet. 2017. Vol. 389, № 10074. P. 1103–1113.Németh G., Laszlovszky I., Czobor P. et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial // The Lancet. 2017. Vol. 389, № 10074. P. 1103–1113.Pásztor Mészáros G., Agai-Csongor E., Kapás M. Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine // Journal of Pharmaceutical and Biomedical Analysis. 2008. Vol. 48, № 2. P. 388–97.Pásztor Mészáros G., Agai-Csongor E., Kapás M. Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine // Journal of Pharmaceutical and Biomedical Analysis. 2008. Vol. 48, № 2. P. 388–97.Reynolds G. P. Histamine and antipsychotic drug-induced weight gain // Journal of Psychopharmacology. 2012. Vol. 26, № 12. P. 1608Reynolds G. P. Histamine and antipsychotic drug-induced weight gain // Journal of Psychopharmacology. 2012. Vol. 26, № 12. P. 1608Richelson E. New antipsychotic drugs: how do their receptor-binding profiles compare? // Journal of Clinical Psychiatry. 2010. Vol. 71, № 9. P. 1243–1244.Richelson E. New antipsychotic drugs: how do their receptor-binding profiles compare? // Journal of Clinical Psychiatry. 2010. Vol. 71, № 9. P. 1243–1244.Roberts R. J., Findlay L. J., El-Mallakh P. L. et al. Update on schizophrenia and bipolar disorder: focus on cariprazine // Neuropsychiatric Disease and Treatment. 2016. Vol. 12. P. 1837–1842.Roberts R. J., Findlay L. J., El-Mallakh P. L. et al. Update on schizophrenia and bipolar disorder: focus on cariprazine // Neuropsychiatric Disease and Treatment. 2016. Vol. 12. P. 1837–1842.Seneca N., Finnema S. J., Laszlovszky I. et al. Occupancy of dopamine D₂ and D₃ and serotonin 5-HT₁A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography // Psychopharmacology. 2011. Vol. 218, № 3. P. 579–587.Seneca N., Finnema S. J., Laszlovszky I. et al. Occupancy of dopamine D₂ and D₃ and serotonin 5-HT₁A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography // Psychopharmacology. 2011. Vol. 218, № 3. P. 579–587.Stahl S. M. Case studies: Stahl's essential psychopharmacology. Cambridge University Press, 2011.Stahl S. M. Case studies: Stahl's essential psychopharmacology. Cambridge University Press, 2011.Stahl S. M. Case Studies: Stahl's Essential Psychopharmacology: Volume 2. Cambridge University Press. 1st ed. 2017.Stahl S. M. Case Studies: Stahl's Essential Psychopharmacology: Volume 2. Cambridge University Press. 1st ed. 2017.Stahl S. M. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press. 6th ed. 2016.Stahl S. M. Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press. 6th ed. 2016.Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. 4th ed. 2013.Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. 4th ed. 2013.Werner F. M., Coveñas R. New developments in the management of schizophrenia and bipolar disorder: potential use of cariprazine // Therapeutics and Clinical Risk Management. 2015. Vol. 11. P. 1657.Werner F. M., Coveñas R. New developments in the management of schizophrenia and bipolar disorder: potential use of cariprazine // Therapeutics and Clinical Risk Management. 2015. Vol. 11. P. 1657.Zimnisky R.б Chang G., Gyertyán I. et al. Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse // Psychopharmacology. 2013. Vol. 226, № 1. P. 91–100.Zimnisky R.б Chang G., Gyertyán I. et al. Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse // Psychopharmacology. 2013. Vol. 226, № 1. P. 91–100.Fleischhacker W., Galderisi S., Laszlovszky I. et al. The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors // European Psychiatry. 2019. Vol. 58. P. 1–9.Fleischhacker W., Galderisi S., Laszlovszky I. et al. The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors // European Psychiatry. 2019. Vol. 58. P. 1–9.Sachs G. Results from three pivotal trials support Vraylar for bipolar I depression [Internet] // Psychiatric Annals. Vol. 45. URL: https://www.healio.com/psychiatry/bipolar-disorder/news/online/%7B6c9e12a4-e17f-4846-b046-6a5731309eee%7D/results-from-three-pivotal-trials-support-vraylar-for-bipolar-i-depression (дата обращения: 11.02.2020).Sachs G. Results from three pivotal trials support Vraylar for bipolar I depression [Internet] // Psychiatric Annals. Vol. 45. URL: https://www.healio.com/psychiatry/bipolar-disorder/news/online/%7B6c9e12a4-e17f-4846-b046-6a5731309eee%7D/results-from-three-pivotal-trials-support-vraylar-for-bipolar-i-depression (дата обращения: 11.02.2020).Allergan, Richter Report Positive Topline Results From Third Cariprazine Trial [Internet]. URL: https://markets.businessinsider.com/news/stocks/allergan-richter-report-positive-topline-results-from-third-cariprazine-trial-1020342427 (дата обращения: 11.02.2020).Allergan, Richter Report Positive Topline Results From Third Cariprazine Trial [Internet]. URL: https://markets.businessinsider.com/news/stocks/allergan-richter-report-positive-topline-results-from-third-cariprazine-trial-1020342427 (дата обращения: 11.02.2020).

The authors declare that there are no conflicts of interest present.