The cerebrovascular, neuroprotective and antiarrhythmic properties of the anxiolytic fabomotizole

Cover Page

Cite item

Full Text

Abstract

Aim. To examine the cerebrovascular, neuroprotective and antiarrhythmic properties of fabomotizole (brand name Afobazole).

Materials and methods. A comprehensive study of fabomotizole's effects on the blood supply, morphology and neuropsychology of the rat brain in various experimental disorders. We recorded cerebral blood flow and studied brain morphology in models of local permanent and global transient ischaemia, haemorrhagic brain damage, combined cerebrovascular and cardiovascular pathology, cardiac arrhythmias, and assessed the neuropsychological status. We measured the levels of GABA, glutamic acid, nerve growth factor, and heat shock protein (HSP70).

Results. Fabomotizole improves blood supply, limits the area of injury, normalizes pathological brain changes in localized cerebral ischaemia, and eliminates neuropsychological damage in models of ischaemic and haemorrhagic stroke. The drug increases cerebral blood flow in ischaemic and haemorrhagic stroke, myocardial infarction and, to a greater extent, in combined cerebrovascular and coronary disease. Fabomotizole acts through the cerebrovascular GABAAergic system, as well as having significant antiarrhythmic properties.

Conclusions. Fabomotizole should be considered not only as an anxiolytic, but also as a drug with potential clinical efficacy in cerebrovascular disease, with concomitant coronary disease and cardiac arrhythmias.

About the authors

Ruben S. Mirzoyan

V.V. Zakusov State Research Institute of Pharmacology

Author for correspondence.
Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-7542-8904
Scopus Author ID: 7006691421

D. Sci. (Med.), Professor, Head, Laboratory of pharmacology of сerebrovascular disorders

Russian Federation, Moscow

Marine G. Balasanyan

M. Heratsi Yerevan State Medical University

Email: cerebropharm@mail.ru
ORCID iD: 0000-0003-4874-9267

D. Sci. (Pharm.), Professor, Head, Department of Pharmacology

Armenia, Yerevan

Hakop V. Topchyan

M. Heratsi Yerevan State Medical University

Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-3079-7896

D. Sci. (Med.), Professor, Head, Department of drug technology

Russian Federation, Yerevan

Vilen P. Hakobyan

M. Heratsi Yerevan State Medical University

Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-5268-0090

D. Sci. (Med.), Professor, Academician of the National Academy of Sciences of the Republic of Armenia, Advisor to the Rector

Russian Federation, Yerevan

Tamara S. Gan'shina

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0003-0442-1761

D. Sci. (Biol.), Professor, leading researcher, Laboratory of pharmacology of сerebrovascular disorders

Russian Federation, Moscow

Nikita A. Khaylov

V.V. Zakusov State Research Institute of Pharmacology; Kurchatov Complex of NBICS Nature-Like Technologies NBC «Kurchatov Institute»

Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-3693-285X

Cand. Sci. (Med.) senior researcher

Russian Federation, Moscow; Moscow

Il'ya N. Kurdyumov

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0003-4251-9217

Cand. Sci. (Biol.), senior researcher, Laboratory of pharmacology of сerebrovascular disorders

Russian Federation, Moscow

Antonina I. Turilova

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-8622-8430

Cand. Sci. (Biol.), senior researcher, Laboratory of pharmacology of сerebrovascular disorders

Russian Federation, Moscow

Тatyana A. Antipova

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0002-9309-4872

Cand. Sci. (Biol.), Head, Laboratory of neuroprotection, Department of pharmacogenetic

Russian Federation, Moscow

Valentina A. Kraineva

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0003-1493-4392

Cand. Sci. (Biol.), senior researcher, Laboratory of psychopharmacology

Russian Federation, Moscow

Sergey B. Seredenin

V.V. Zakusov State Research Institute of Pharmacology

Email: cerebropharm@mail.ru
ORCID iD: 0000-0003-4482-9331

D. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, Scientific supervisor

Russian Federation, Moscow

References

  1. Середенин С.Б., Воронин М.В. Нейрорецепторные механизма действия афобазола. Экспериментальная и клиническая фармакология. 2009; 72(1): 3–11. Seredenin S.B., Voronin M.V. Neuroreceptor mechanisms involved in the action of afobazole. Eksperimental’naya i klinicheskaya farmakologiya. 2009; 72(1): 3–11. (In Russ.)
  2. Антипова Т.А., Сапожникова Д.С., Бахтина Л.Ю., Середенин С.Б. Селективный анксиолитик афобазол увеличивает содержание BDNF и NGF в культуре гиппокампальных нейронов линии НТ-22. Экспериментальная и клиническая фармакология. 2009; 72(1): 12–14. Antipova T.A., Sapozhnikova D.S., Bakhtina L.Yu., Seredenin S.B. Selective anxiolitic afobazole increases the content of BDNF and NGF in the culture of hippocampal HT-22 life neurons. Eksperimental’naya i klinicheskaya farmakologiya. 2009; 72(1): 12–14. (In Russ.)
  3. Середенин С.Б., Мелкумян Д.С., Вальдман Е.А. и др. Влияние афобазола на содержание BDNF в структурах мозга инбредных мышей с различным фенотипом эмоционально-стрессовой реакции. Экспериментальная и клиническая фармакология. 2006; 69(3): 3–6. Seredenin S.B., Melkumyan D.S., Val’dman E.A., et al. Effect of afobazole on the BDNF content in brain structures of inbred mice with different phenotypes of emotional stress reaction. Eksperimental’naya i klinicheskaya farmakologiya. 2006; 69(3): 3–6. (In Russ.)
  4. Voronin M.V., Kadnikov I.A., Voronkov D.N., Seredenin S.B. Chaperone Sigma1R mediates the neuroprotective action of afobazole in the 6-OHDA model of Parkinson’s disease. Sci. Rep. 2019; 9(1): 17020. doi: 10.1038/s41598-019-53413-w
  5. Kadnikov I.A., Verbovaya E.R., Voronkov D.N. et al. Deferred administration of afobazole induces Sigma1R-dependent restoration of striatal dopamine content in a mouse model of Parkinson’s disease. Int. J. Mol. Sci. 2020; 21(20): 7620. doi: 10.3390/ijms21207620
  6. Воронин М.В., Кадников И.А., Абрамова Е.В. Молекулярные механизмы нейротропного действия афобазола. Экспериментальная и клиническая фармакология. 2021; 84(2): 15–22. Voronin1 M.V., Kadnikov I.A., Abramova E.V. Molecular mechanisms of afobazole neurotropic action. Eksperimental’naya i klinicheskaya farmakologiya. 2021; 84(2): 15–22. (In Russ.) doi: 10.30906/0869-2092-2021-84-2-15-22
  7. de la Torre J.C. Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer’s disease. J. Alzheimers Dis. 2012; 32(3): 553–567. doi: 10.3233/JAD-2012-120793
  8. Neumann J.T., Cohan C.H., Dave K.R. et al. Global cerebral ischemia: synaptic and cognitive dysfunction. Curr. Drug Targets. 2013; 14(1): 20–35. doi: 10.2174/138945013804806514
  9. Duncombe J., Kitamura A., Hase Y. et al. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin. Sci. (Lond). 2017; 131(19): 2451–2468. doi: 10.1042/CS20160727
  10. Smith E.E., Cieslak A., Barber P. et al. Therapeutic strategies and drug development for vascular cognitive impairment. J. Am. Heart Assoc. 2017; 6(5): e005568. doi: 10.1161/JAHA.117.005568
  11. Aires A., Andrade A., Azevedo E. et al. Neurovascular coupling impairment in heart failure with reduction ejection fraction. Brain Sci. 2020; 10(10): 714. DOI: 10.3390 /brainsci10100714
  12. Ovsenik A., Podbregar M., Fabjan A. Cerebral blood flow impairment and cognitive decline in heart failure. Brain Behav. 2021; 11(6): e02176. doi: 10.1002/brb3.2176
  13. Park J. (ed.). Acute ischemic stroke. acute ischemic stroke medical, endovascular, and surgical techniques. Springer; 2017. 270 p.
  14. Пирадов М.А., Танашян М.М., Максимова М.Ю. (ред.) Инсульт: современные технологии диагностики и лечения. М.; 2018; 360 с. Piradov M.A., Tanashyan M.M., Maksimova M.Yu. (eds.) Stroke: modern diagnostic and treatment technologies. Moscow; 2018. 360 p. (In Russ.)
  15. Мирзоян Р.С., Ганьшина Т.С., Ким Г.А. и др. Трансляционный потенциал экспериментальной фармакологии цереброваскулярных расстройств. Анналы клинической и экспериментальной неврологии. 2019; 13(3): 34–40. Mirzoian R.S., Gan’shina Т.S., Kim G.A. et al. The translational potential of experimental pharmacology for cerebrovascular disorders. Annals of clinical and experimental neurology. 2019; 13(3): 34–40. (In Russ.) doi: 10.25692/ACEN. 2019.3.5
  16. Shafie M., Yu W. Recanalization therapy for acute ischemic stroke with large vessel occlusion: where we are and what comes next? Transl. Stroke Res. 2021; 12(3): 369–381. doi: 10.1007/s12975-020-00879-w
  17. Virani S.S., Alonso A., Aparicio H.J. et al. Heart Disease and Stroke Statistics-2021 update: a report from the American Heart Association. Circulation. 2021; 143(8): e254–e743. doi: 10.1161/CIR.0000000000000950
  18. Tamura A., Graham D.I., McCulloch J., Teasdale G.M. Focal cerebral ischae- mia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J. Cereb. Blood Flow Metab. 1981; 1(1): 53–60. doi: 10.1038/jcbfm.1981.6
  19. Топчян А.В., Мирзоян Р.С., Баласанян М.Г. Локальная ишемия мозга крыс, вызванная перевязкой средней мозговой артерии. Экспериментальная и клиническая фармакология. 1996; 59(5): 62–64. Topchian A.V., Mirzoian R.S., Balasanian M.G. Local cerebral ischemia in rats induced by ligation of the middle cerebral artery. Eksperimental’naya i klinicheskaya farmakologiya. 1996; 59(5): 62–64. (In Russ.)
  20. Мирзоян Р.С., Топчян А.В., Канаян А.С., Баласанян М.Г. Влияние нимодипина на локальное ишемическое поражение мозга. Вестник Российской академии медицинских наук. 1998; (11): 46–51. Mirzoian R.S., Topchian A.V., Kanaian A.S., Balasanian M.G. The effect of nimodipine on a local ischemic brain lesion. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk. 1998; (11): 46–51. (In Russ.)
  21. Баласанян М.Г. Изучение роли оксида азота в механизмах нейропротекторного и анксиолитического действия афобазола в сравнительном аспекте. Автореф. дис. … докт. мед докторской диссертации. Ереван; 2003. Balasanyan M.G. Study of the role of nitric oxide in the mechanisms of neuroprotective and anxiolytic action of afobazole in a comparative aspect. Abstract … dis. D. Sci. (Med.). Yerevan; 2003. (In Russ.)
  22. Баласанян М.Г., Канаян А.С., Топчян А.В., Акопян В.П. Нейропротекторная способность афобазола в защите ишемизированного мозга. Экспериментальная и клиническая фармакология. 2021; 84(2): 23-27. Balasanyan M.G., Kanayan A.S., Topchyan H.V., Hakobyan V.P. Neuroprotective activity of afobazole in ischemized brain. Eksperimental’naya i klinicheskaya farmakologiya. 2021; 84(2): 23-27. (In Russ.) doi: 10.30906/0869-2092-2021-84-2-23-27.
  23. Середенин С.Б., Поварова О.В., Медведев О.С. и др. Доказательство нейропротекторных свойств афобазола на экспериментальной модели фокальной ишемии головного мозга. Экспериментальная и клиническая фармакология. 2006; 69(4): 3–5. Seredenin S.B., Povarova O.V., Medvedev O.S., et al. Evidence of the neuroprotective properties of afobazole in an experimental model of focal cerebral ischemia. Eksperimental’naya i klinicheskaya farmakologiya. 2006; 69(4): 3–5. (In Russ.)
  24. Силкина И.В., Ганьшина Т.С., Середенин С.Б., Мирзоян Р.С. ГАМК-ергический механизм цереброваскулярного и нейропротекторного эффектов афобазола и пикамилона. Экспериментальная и клиническая фармакология. 2005; 68(1): 20–24. Silkina I.V., Ganshina T.S., Seredenin S.B., Mirzoyan R.S. GABA-ergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon. Eksperimental’naya i klinicheskaya farmakologiya. 2005; 68(1): 20–24. (In Russ.)
  25. Kim J.Y., Kim J.W., Yenari M.A. Heat shock protein signaling in brain ischemia and injury. Neurosci. Lett. 2020; 715: 134642. doi: 10.1016/j.neulet.2019.134642
  26. Yang J., Wu S., Hou L. et al. Therapeutic effects of simultaneous delivery of nerve growth factor mRNA and protein via exosomes on cerebral ischemia. Mol. Ther. Nucleic Acids. 2020; 21: 512–522. doi: 10.1016/j.omtn.2020.06.013
  27. Курдюмов И.Н. Цереброваскулярные эффекты ГАМК-ергических веществ в условиях геморргического и ишемического поражений мозга. Автореф. дис. … канд. биол. наук. М.; 2009. Kurdyumov I.N. Cerebrovascular effects of GABA-ergic substances in conditions of hemorrhagic and ischemic brain lesions. Abstract dis. … Cand. Sci. (Biol.). Moscow; 2009. (In Russ.)
  28. Байкова В.С., Кадников И.А., Воронин М.В. и др. Влияние афобазола на содержание нейромедиаторных аминокислот в стриатуме крыс при глобальной преходящей ишемии. Бюллетень экспериментальной биологии и медицины. 2011; 151(5): 526–529.Baykova V.S., Kadnikov I.A., Voronin M.V., Ganshina T.S., Gnezdilova A.V., Gorbunov A.A., Mirzoyan R.S., Seredenin S.B. Effect of afobazole on the content of neurotransmitter amino acids in the striatum in global transient ischemia. Bulletin of Experimental Biology and Medicine. 2011; 151(5): 526–529. (In Russ.)
  29. Lindley R.I., Wardlaw J.M.., Sandercock PA. et al. Frequency and risk factors for spontaneous hemorrhagic transformation of cerebral infarction. J. Stroke Cerebrovasc. Dis. 2004; 13(6): 235–246. doi: 10.1016/j.jstrokecerebro vasdis.2004.03.003
  30. Andrade J.B.C., Mohr J.P., Lima F.O. et al. Predictors of hemorrhagic transformation after acute ischemic stroke based on the experts’ opinion. Arq. Neuropsiquiatr. 2020; 78(7): 390–396. doi: 10.1590/0004-282x20200008
  31. Venditti L., Chassin O., Ancelet C. et al. Pre-procedural predictive factors of symptomatic intracranial hemorrhage after thrombectomy in stroke. J. Neurol. 2021; 268(5):1867–1875. doi: 10.1007/s00415-020-10364-x
  32. Макаренко А.Н., Косицын Н.С., Пасикова Н.В., Свинов М.М. Метод моделирования локального кровоизлияния в различных структурах головного мозга у экспериментальных животных. Журнал высшей нервной деятельности им. И.П. Павлова. 2002; 52(6): 765–768. Makarenko A.N., Kositsyn N.S., Pasikova N.V., Svinov M.M. A method for modeling local hemorrhage in various brain structures in experimental animals. Zhurnal vysshey nervnoy deyatel’nosti im. I.P. Pavlova. 2002; 52(6): 765–768. (In Russ.)
  33. Мирзоян Н.Р., Ганьшина Т.С., Курдюмов И.Н., Беро Р.С. Влияние противоишемической комбинации и нимодипина на кровоснабжение мозга крыс в условиях модели геморрагического инсульта. Экспериментальная и клиническая фармакология. 2008; 71(2): 17–20. Mirzoyan N.R., Gan’shina T.S., Kurdyumov I.N., Bero R.S. Effects of an antiischemic combination and nimodipine on the blood supply to the brain of rats in a model of hemorrhagic stroke. Eksperimental’naya i klinicheskaya farmakologiya. 2008; 71(2): 17–20. (In Russ.)
  34. Середенин С.Б., Крайнева В.А. Нейропротекторные свойства афобазола при экспериментальном моделировании геморрагического инсульта. Экспериментальная и клиническая фармакология. 2009; 72(1): 24–28. Seredenin S.B., Kraineva V.A. Neuroprotective effects of afobazole on a hemorrhagic stroke model. Eksperimental’naya i klinicheskaya farmakologiya. 2009; 72(1): 24–28. (In Russ.)
  35. Ганьшина Т.С., Курдюмов И.Н., Турилова А.И. и др. Влияние афобазола на кровоснабжение мозга в условиях модели геморрагического инсульта. Экспериментальная и клиническая фармакология. 2009; 72(6): 18–21. Gan’shina T.S., Kurdyumov I.N., Turilova A.I. et al. Afobazole effect on cerebral circulation under hemorrhagic stroke model conditions. Eksperimental’naya i klinicheskaya farmakologiya. 2009; 72(6): 18–21. (In Russ.)
  36. Seropian I.M., Gonzales G.E. In: A. Rigalli, V.E. Di Loreto (eds.) Experimental surgical models in the laboratory rat. Boca Raton. London. New York; 2009: 201–204.
  37. Лебедева М.А., Медведева, Мирзоян Р.С. и др. Интегральная оценка сдвигов в сывороточном гомеостазе при экспериментальном инфаркте миокарда. Патологическая физиология и экспериментальная терапия. 2013; 57(4): 35–40. Lebedeva M.A.,Medvedeva U.S., Mirzoyan R.S. et al. Integrated assessment of serum homeostasis shifts in experimental myocardial infarction. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2013; 57(4): 35–40. (In Russ.)
  38. Gunnoo T., Hasan N., Khan M.S. et al. Quantifying the risk of heart disease following acute ischaemic stroke: a meta-analysis of over 50,000 participants. BMJ Open. 2016; 6(1): e009535. doi: 10.1136/bmjopen-2015-009535
  39. Bhatia R., Sharma G., Patel C. et al. Coronary artery disease in patients with ischemic stroke and TIA. J. Stroke Cerebrovasc. Dis. 2019; 28(12): 104400. doi: 10.1016/j.jstrokecerebrovasdis.2019.104400
  40. Albaeni A., Harris C.M., Nasser H. et al. In-Hospital acute ischemic stroke following ST-elevation myocardial infarction. Int. J. Cardiol. Heart Vasc. 2020; 31: 100684. doi: 10.1016/j.ijcha.2020.100684
  41. Aggarwal G., Patlolla S.H., Aggarwal S. et al. Temporal trends, predictors, and outcomes of acute ischemic stroke in acute myocardial infarction in the United States. J. Am. Heart Assoc. 2021; 10(2): e017693. doi: 10.1161/JAHA.120.017693
  42. Мирзоян Р.С., Ганьшина Т.С., Хайлов Н.А. и др. Цереброваскулярная фармакология раздельной и сочетанной сосудистой патологии мозга и сердца. Экспериментальная и клиническая фармакология. 2014; 77(3): 3–8. Mirzoyan R.S., Gan’shina Т.S., Khaylov N.A. et al., Cerebrovascular pharmacology of separate and combined vascular pathology of brain and heart. Eksperimental’naya i klinicheskaya farmakologiya. 2014; 77(3): 3–8. (In Russ.)
  43. Мирзоян Р.С., Хайлов Н.А., Ганьшина Т.С. Цереброваскулярные эффекты афобазола при сочетанной сосудистой патологии мозга и сердца. Экспериментальная и клиническая фармакология. 2010; 73(5): 2–7. Mirzoyan R.S., Khailov N.A., Gan’shina T.S. Cerebrovascular effects of afobazole under combined disorders of cerebral and coronary circulation. Eksperimental’naya i klinicheskaya farmakologiya. 2010; 73(5): 2–7. (In Russ.)
  44. Eckardt M., Gerlach L., Welter F.L. Prolongation of the frequency-corrected QT dispersion following cerebral strokes with involvement of the insula of Reil. Eur. Neurol. 1999; 42(4): 190–193. doi: 10.1159/000008105
  45. Lederman Y.S., Balucani C., Lazar J. et al. Relationship between QT interval dispersion in acute stroke and stroke prognosis: a systematic review. J. Stroke Cerebrovasc. Dis. 2014; 23(10): 2467–2478. doi: 10.1016/j.jstrokecer ebrovasdis.2014.06.004
  46. Emektar E., Çorbacıoğlu Ş.K., Korucu O. et al. The evaluation of a new marker of transmyocardial repolarization parameters in ischemic stroke patients; T peak-T end (T p-e), T p-e/QTc. Acta Neurol. Belg. 2017; 117(2): 461–467. doi: 10.1007/s13760-017-0744-4.
  47. Danese A., Cappellari M., Pancheri E. et al. The dispersion of myocardial repolarization in ischemic stroke and intracranial hemorrhage. J. Electrocardiol. 2018; 51(4): 691–695. doi: 10.1016/j.jelectrocard.2018.05.007
  48. Lian H., Xu X., Shen X. et al. Early prediction of cerebral-cardiac syndrome after ischemic stroke: the PANSCAN scale. BMC Neurol. 2020; 20(1): 272. doi: 10.1186/s12883-020-01833-x
  49. Галенко-Ярошевский П.А., Каверина Н.В., Камкин А.Г. и др. Методические рекомендации по доклиническому изучению антиаритмических лекарственных средств. В кн.: А.Н. Миронов (ред.) Руководство по проведению доклинических исследований лекарственных средств. М.; 2012; 1: 385–416. Galenko-Yaroshevsky P.A., Kaverina N.V., Kamkin A.G. Methodical recommendations for the preclinical study of antiarrhythmic drugs. In: A.N. Mironov (ed.) Guidelines for conducting preclinical studies of drugs. Moscow; 2012; 1: 385–416. (In Russ.)
  50. Vaughan Williams E.M. In: L. Szekeres (ed.) Pharmacology of antiarhrythmic agents. Oxford; 1981: 125–150.
  51. Турилова А.И., Можаева Т.Я. Антиаритмические свойства афобазола и других производных 2-меркаптобензимидазола. Экспериментальная и клиническая фармакология. 2010; 73(5): 8–11. Turilova A.I., Mozhaeva T.Y. Antiarrhythmic properties of afobazole and other derivatives of 2-mercaptobenzimidazole. Eksperimental’naya i klinicheskaya farmakologiya. 2010; 73(5): 8–11. (In Russ.)
  52. Ким Г.А., Ганьшина Т.С., Васильева Е.В. и др. ГАМКА-рецепторные механизмы противоишемического цереброваскулярного эффекта S-амлодипина никотината. Экспериментальная и клиническая фармакология. 2017; 80(5): 7–10. Kim G.A., Gan’shina T.S., Vasil’eva E. V. et al. GABAA receptor mechanism of anti-ishemic cerebrovascular effect of S-amlodipine nicotinate. Eksperimental’naya i klinicheskaya farmakologiya. 2017; 80(5): 7–10. (In Russ.)
  53. Мирзоян Р.С., Ганьшина Т.С. Фармакология цереброваскулярных заболеваний и мигрени (сходство и различия). M.; 2022. 370 с. Mirzoyan R.S., Gan’shina T.S. Pharmacology of cerebrovascular diseases and migraine (similarities and differences). Moscow; 2022. 370 p. (In Russ.)
  54. Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J. Appl. Physiol. 1985. 2006; 100(3): 1059–1064. DOI: 10.1152/ japplphysiol.00954.2005
  55. Kocharyan A., Fernandes P., Tong X.K. et al. Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation. J. Cereb. Blood Flow Metab. 2008; 28(2): 221–231. doi: 10.1038/sj.jcbfm.9600558
  56. Lecrux C., Hamel E. The neurovascular unit in brain function and disease. Acta Physiol. (Oxf.). 2011; 203(1): 47–59. doi: 10.1111/j.1748- 1716.2011.02256.x
  57. Hamel E., Krause D.N., Roberts E. Characterization of glutamic acid decarboxylase activity in cerebral blood vessels. J. Neurochem. 1982; 39(3): 842–849. doi: 10.1111/j.1471-4159.1982.tb07969.x
  58. Мирзоян С.А. Нейрохимический контроль мозгового кровообращения. Фармакология и токсикология. 1983; 46(4): 5–15. Mirzoyan S.A. Neurochemical control of cerebral circulation. Pharmacology and toxicology. 1983; 46(4): 5–15. (In Russ.)
  59. Масленников Д.В., Ганьшина Т.С., Олейникова О.Н. и др. ГАМК-ергический механизм цереброваскулярного эффекта мелатонина. Экспериментальная и клиническая фармакология. 2012; 75(4): 13–16. Maslennikov D.V., Ganshina T.S., Oleinikova O.N. et al. GABAergic mechanism of the cerebrovascular effect of melatonin. Eksperimental’naya i klinicheskaya farmakologiya. 2012; 75(4): 13–16. (In Russ.)
  60. Chu U.B., Ruoho A.E. Biochemical pharmacology of the sigma-1 receptor. Mol. Pharmacol. 2016; 89(1): 142–153. doi: 10.1124/mol.115.101170
  61. Morales-Lázaro S.L., González-Ramírez R., Rosenbaum T. Molecular interplay between the sigma-1 receptor, steroids, and ion channels. Front. Pharmacol. 2019; 10: 419. doi: 10.3389/fphar.2019.00419
  62. Aishwarya R., Abdullah C.S., Morshed M. et al. Sigmar1’s molecular, cellular, and biological functions in regulating cellular pathophysiology. Front. Physiol. 2021;12: 705575. doi: 10.3389/fphys.2021.705575
  63. Goyagi T., Bhardwaj A., Koehler R.C. et al. Potent sigma 1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine provides ischemic neuroprotection without altering dopamine accumulation in vivo in rats. Anesth. Analg. 2003; 96(2): 532–538. doi: 10.1097/00000539-200302000-00043
  64. Luedtke R.R., Perez E., Yang S.H. et al. Neuroprotective effects of high affinity sigma-1 receptor selective compounds. Brain Res. 2012; 1441: 17–26. doi: 10.1016/j.brainres.2011.12.047
  65. Penke B., Fulop L., Szucs M., Frecska E. The role of sigma-1 receptor, an intracellular chaperone in neurodegenerative diseases. Curr. Neuropharmacol. 2018; 16(1): 97–116. doi: 10.2174/1570159X15666170529104323
  66. Ryskamp D.A., Korban S., Zhemkov V. et al. Neuronal sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases. Front. Neurosci. 2019; 13: 862. doi: 10.3389/fnins.2019.00862
  67. Pellavio G., Rossino G., Gastaldi G. et al. Sigma-1 receptor agonists acting on aquaporin-mediated H2O2 permeability: new tools for counteracting oxidative stress. Int. J. Mol. Sci. 2021; 22(18): 9790. doi: 10.3390/ijms22189790
  68. Xu Q., Ji X.F., Chi T.Y. et al. Sigma 1 receptor activation regulates brain-derived neurotrophic factor through NR2A-CaMKIV-TORC1 pathway to rescue the impairment of learning and memory induced by brain ischaemia/reperfusion. Psychopharmacology (Berl). 2015; 232(10): 1779–1791. doi: 10.1007/s00213-014-3809-6
  69. Xu Q., Ji X.F., Chi T.Y. et al. Sigma-1 receptor in brain ischemia/reperfusion: Possible role in the NR2A-induced pathway to regulate brain-derived neurotrophic factor. J. Neurol. Sci. 2017; 376: 166–175. doi: 10.1016/j.jns.2017.03.027
  70. Liu D.Y., Chi T.Y., Ji X.F. et al. Sigma-1 receptor activation alleviates blood- brain barrier dysfunction in vascular dementia mice. Exp. Neurol. 2018; 308: 90–99. doi: 10.1016/j.expneurol.2018.07.002
  71. Sałaciak K., Pytka K. Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders. Neurosci. Biobehav. Rev. 2021; 132: 1114–1136. doi: 10.1016/j.neubiorev.2021.10.037
  72. Martin P., Reeder T., Sourbron J. et al. An emerging role for sigma-1 receptors in the treatment of developmental and epileptic encephalopathies. Int. J. Mol. Sci. 2021; 22(16): 8416. doi: 10.3390/ijms22168416
  73. Vavers E., Zvejniece B., Stelfa G. et al. Genetic inactivation of the sigma-1 chape- rone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased susceptibility to seizures. Neurobiol. Dis. 2021; 150: 105244. doi: 10.1016/j.nbd.2020.105244
  74. Voronin M.V., Vakhitova Y.V., Seredenin S.B. Chaperone sigma1r and antidepressant effect. Int. J. Mol. Sci. 2020; 21(19): 7088. doi: 10.3390/ijms21197088
  75. Shinoda Y., Tagashira H., Bhuiyan M.S. et al. Corticosteroids mediate heart failure-induced depression through reduced σ1-receptor expression. PLoS One. 2016; 11(10): e0163992. doi: 10.1371/journal.pone.0163992
  76. Yoon S.Y., Roh D.H., Seo H.S. et al. Intrathecal injection of the neurosteroid, DHEAS, produces mechanical allodynia in mice: involvement of spinal sigma-1 and GABA receptors. Br. J. Pharmacol. 2009; 157(4): 666–673. doi: 10.1111/j.1476-5381.2009.00197.x
  77. Ago Y, Hasebe S, Hiramatsu N. et al. Involvement of GABAA receptors in 5-HT1A and σ1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency. Psychopharmacology (Berl). 2016; 233(17): 3125–3134. doi: 10.1007/s00213-016-4353-3
  78. Hasebe S., Ago Y., Watabe Y. et al. Anti-anhedonic effect of selective serotonin reuptake inhibitors with affinity for sigma-1 receptors in picrotoxin-treated mice. Br. J. Pharmacol. 2017; 174(4): 314–327. doi: 10.1111/bph.13692
  79. Tuem K.B., Atey T.M. Neuroactive steroids: receptor interactions and responses. Front. Neurol. 2017; 8: 442. doi: 10.3389/fneur.2017.00442

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. The effect of fabomotizole (А) and nimodipine (В) on changes (%) in loca- lized cerebral blood flow in intact rats (1), in experimental myocardial infarction (2), haemorrhagic stroke (3), transient global cerebral ischaemia (4), and combined cerebrovascular and cardiovascular disease (5).

Download (162KB)
Indexing metadata

Copyright (c) 2022 Mirzoyan R.S., Balasanyan M.G., Topchyan H.V., Hakobyan V.P., Gan'shina T.S., Khaylov N.A., Kurdyumov I.N., Turilova A.I., Antipova Т.A., Kraineva V.A., Seredenin S.B.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies