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Volchegorskii I.A.

South Ural State Medical University

Rassokhina L.M.

South Ural State Medical University

Miroshnichenko I.U.

South Ural State Medical University

Possibilities of «therapeutic retargeting» of 3-hydroxypyridine and succinic acid derivatives due to their dopaminergic action

Authors:

Volchegorskii I.A., Rassokhina L.M., Miroshnichenko I.U.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(3): 17‑26

DOI: 10.17116/jnevro202412403117

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POSSIBILITIES OF «THERAPEUTIC RETARGETING» OF 3-HYDROXYPYRIDINE AND SUCCINIC ACID DERIVATIVES DUE TO THEIR DOPAMINERGIC ACTION
POSSIBILITIES OF «THERAPEUTIC RETARGETING» OF 3-HYDROXYPYRIDINE AND SUCCINIC ACID DERIVATIVES DUE TO THEIR DOPAMINERGIC ACTION

To cite this article:

Volchegorskii IA, Rassokhina LM, Miroshnichenko IU. Possibilities of «therapeutic retargeting» of 3-hydroxypyridine and succinic acid derivatives due to their dopaminergic action. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(3):17‑26. (In Russ.)
https://doi.org/10.17116/jnevro202412403117

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
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Abstract:

The review is devoted to a comparative analysis of the clinical efficacy of the original domestic derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) in comparison with the results of an experimental study of their dopaminergic action. The position that the dopaminomimetic activity of emoxipin, reamberin and mexidol largely determines their anti-ischemic, antihypoxic, insulin-potentiating neuroprotective, nootropic and antidepressant potential has been substantiated. A comparative analysis of the safety profile of emoxipine, reamberin and mexidol was carried out, taking into account potential and real side-effects caused by iatrogenic deviations from the eudopaminergic state. It has been shown that mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which is simultaneously a derivative of 3-hydroxypyridine and succinic acid, has the best balance of efficacy and safety. A generalized assessment of the available data on the successful use of off-label derivatives of 3-hydroxypyridine and succinic acid indicates the advisability of a significant expansion of indications for their clinical use. The authors resume that the «therapeutic retargeting» of emoxipin, reamberin and mexidol (i.e. their use for qualitatively new indications) will contribute to progress in the treatment of socially significant and most common diseases.

Keywords:

3-hydroxypyridine and succinic acid derivatives
dopaminergic action
«therapeutic retargeting»
socially significant and most common diseases

Authors:

Volchegorskii I.A.

South Ural State Medical University

Rassokhina L.M.

South Ural State Medical University

Miroshnichenko I.U.

South Ural State Medical University

Received:

29.03.2023

Accepted:

12.12.2023

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References:

  1. Pozhilova EV, Novikov VE, Novikova AV. Pharmacodynamics and clinical applications of preparations based on hydroxypyridine. Vestnik Smolenskoi Gosudarstvennoi Meditsinskoi Akademii. 2013;12(3):56-66. (In Russ.).
  2. Shakhmardanova SA, Gulevskya ON, Khananashvili YaA, et al. Succinic and fumaric acid drugs for prevention and treatment of various diseases. Zhurnal Fundamentalnoi Meditsini i Biologii. 2016;(3):16-30. (In Russ.).
  3. Voronina TA. Pioneer of antioxidant neuroprotection. 20 years in clinical practice. Russkii Meditsinskii Zhurnal. 2016;24(7):434-438. (In Russ.).
  4. Volchegorskii IA, Mester KM. Effects of 3-hydroxypyridine and succinic acid derivatives on the dynamics of dorsalgia and affective disorders after surgical treatment of disc herniation. Eksperimental’naya i Klinicheskaya Farmakologiya. 2010;73(1):33-39. (In Russ.).
  5. Volchegorskii IA, Pravdin EV, Uzlova TV. Effect of 3-oxypyridine and succinic acid derivatives on affective status in recrudescence of inflammatory diseases of uterus and its appendages. Eksperimental’naya i Klinicheskaya Farmakologiya. 2012;75(11):22-27. (In Russ.).
  6. Volchegorskii IA, Vazhenin AV, Zyuzina MS. The effect of derivatives of 3-hydroxypyridine and succinic acids on depressive symptoms, pain intensity and quality of life after surgical treatment of breast cancer. Sovremennaya Onkologiya. 2018;20(1):54-59. (In Russ.).
  7. Novikov VE, Levchenkova OS, Ivantsova EN. Possibilities of antihypoxant use for mitochondrial dysfunctions. Vestnik Smolenskoi Gosudarstvennoi Meditsinskoi Akademii. 2020;19(1):41-55. (In Russ.).
  8. Nosal’ LA, Simonova NV, Dorovskikh VA. Experience of using reamberin on the cognitive functions in children with epilepsy. Zhurnal Nevrologii i Psikhiatrii im. C.C. Korsakova. 2020;120(11):53-58. (In Russ.). https://doi.org/10.17116/jnevro202012011153
  9. Volchegorskii IA, Izarovskii BV, Shamaeva TN. The effect of 3-oxypyridine and succinic acid derivatives on the dynamics of clinical manifestations of alcohol withdrawal syndrome during the course of standard treatment. Voprosy Narkologii. 2020;8(191):24-46. (In Russ.). https://doi.org/10.47877/0234-0623_2020_08_24
  10. Volchegorskii IA, Vazhenin AV, Alekseeva AP. The effect of hydrochloric, malic and succinic salts of 2-ethyl-6-methyl-3-oxypyridine on self-assessment of depression manifestations in women receiving radiotherapy after surgical treatment of uterine cancer. Kazanskii Meditsinskii Zhurnal. 2022;103(6):937-946. (In Russ.). https://doi.org/10.17816/KMJ105189
  11. Volchegorskii IA, Minochkin PI, Volosnikov DK. Efficiency of emoxipine in treating multiple organ failure in newborns. Eksperimental’naya i Klinicheskaya Farmakologiya. 2010;73(9):34-38. (In Russ.).
  12. Novoselov PN, Volchegorskii IA, Astakhova TV. New possibilities of using ascorbic acid and emoxypine in the treatment of infiltrative pulmonary tuberculosis. Tuberkulez i Bolezni Legkikh. 2011;88(5):79. (In Russ.).
  13. Rudrapal M, Khairnar SJ, Jadhav AG. Drug Repurposing (DR): An Emerging Approach in Drug Discovery. In: Badria FA, ed. Drug Repurposing. Hypothesis, Molecular Aspects and Therapeutic Applications. [S.l.]: IntechOpen; 2020;1-20.  https://doi.org/10.5772/intechopen.93193
  14. Okovity SV, Sukhanov DS, Zaplutanov VA, et al. Antihypoxants in current clinical practice. Klinicheskaya Meditsina. 2012;90(9):63-68. (In Russ.).
  15. Volchegorskii IA, Miroshnichenko IU, Rassokhina LM, et al. The effect of 3-hydroxypiridine and succinic acid derivatives on the physical performance of mice and their resistance to acute hypoxia of different origins. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2019;105(3):363-374. (In Russ.). https://doi.org/10.1134/S0869813919030099
  16. Volchegorskiĭ IA, Miroshnichenko IIu, Rassokhina LM, et al. The effect of 3-oxypiridine and succinic acid derivatives on the resistance to acute cerebral ischemia. Zhurnal Nevrologii i Psikhiatrii im. C.C. Korsakova. 2014;114(12):123-127. (In Russ.). https://doi.org/10.17116/jnevro2014114121123-127
  17. Volchegorskii IA, Miroshnichenko IY, Rassokhina LM. Effects of 3-hydroxypyridine and succinic acid derivatives on resistance to acute adrenaline intoxication and formalin edema in mice. Khimiko-Farmatsevticheskii Zhurnal. 2014;48(9):3-6. (In Russ.). https://doi.org/10.30906/0023-1134-2014-48-9-3-6
  18. Novikova LB, Sharapova KM, Sharafutdinova LR. The use of Mexidol in the acute and acute periods of ischemic stroke. Terapiya. 2019;5(S):226-229. (In Russ.).
  19. Privalov AA, Kholmanskikh NV, Obukhov NG. Use of reamberin in treatment of patients with the disorders of cerebral circulation of ischemic type. Vestnik Sankt-Peterburgskoi Gosudarstvennoi Meditsinskoi Akademii im. I.I. Mechnikova. 2006;7(1):102-105. (In Russ.).
  20. Volchegorskii IA, Miroshnichenko IYu, Rassokhina LM, et al. The effect of 3-hydroxypyridine and succinic acid derivatives on stereotypic behavior and catalepsy in mice. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2017;103(4):406-416. (In Russ.).
  21. Kulinskii VI, Usov LA, Sufianova GZ, et al. Comparative characteristics and receptor mechanism of the effect of adenosine receptor agonists in complete cerebral ischemia. Eksperimental’naya i Klinicheskaya Farmakologiya. 1993;56(6):13-16. (In Russ.).
  22. Lalley PM. Opioidergic and dopaminergic modulation of respiration. Respiratory Physiology & Neurobiology. 2008;164(1-2):160-167.  https://doi.org/10.1016/j.resp.2008.02.004
  23. Volchegorskii IA, Sinitskii AI, Miroshnichenko IY, et al. Effects of 3-hydroxypyridine and succinic acid derivatives on monoamine oxidase activity in vitro. Pharmaceutical Chemistry Journal. 2018;52(1):3-7. (In Russ.). https://doi.org/10.30906/0023-1134-2018-52-1-3-7
  24. Graves SM, Xie Z, Stout KA, et al. Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain. Nature neuroscience. 2020;23(1):15-20.  https://doi.org/10.1038/s41593-019-0556-3
  25. Volchegorsky IA, Moskvicheva MG, Chashchina YeN. Efficacy of derivatives of 3-hydroxypyridine and succinic acid in diabetic patients with the diabetic foot. Klinicheskaya Meditsina. 2004;82(11):31-35. (In Russ.).
  26. Orlova VA, Voskresenskaya NI. Mexidol: treatment of depressive and neurosis-like disorders in schizophrenia. Psikhiatriya. 2004;5(11):42-49. (In Russ.).
  27. Volchegorskii IA, Miroshnichenko IYu, Rassohina LM, et al. Experimental study of 3-oxypiridine and succinic acid derivates antidepressant activity in mice Eksperimental’naya i Klinicheskaya Farmakologiya. 2013;76(7):6-10. (In Russ.).
  28. Volchegorskiĭ IA, Miroshnichenko IIu, Rassokhina LM, et al. Antidepressant effect of 3-oxypyridine and succinic acid derivatives (experimental study). Zhurnal Nevrologii i Psikhiatrii im. C.C. Korsakova. 2015;115(2):48-52. (In Russ.). https://doi.org/10.17116/jnevro20151152148-52.
  29. Volchegorskii IA, Miroshnichenko IYu, Rassokhina LM. Acute antidepressive effect of 3-oxypiridine and succinic acid derivatives in experimental study on rats. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2017;103(7):755-767. (In Russ.).
  30. Volchegorskii IA, Miroshnichenko IYu, Rassokhina LM, et al. Antianhedonic effect of 3-oxypyridine and succinic acid derivatives. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2016;102(11):1312-1322. (In Russ.).
  31. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American Journal of Psychiatry. 2006;163(11):1905-1917. https://doi.org/10.1176/ajp.2006.163.11.1905
  32. Berridge KC, Kringelbach ML. Pleasure systems in the brain. Neuron. 2015;86(3):646-664.  https://doi.org/10.1016/j.neuron.2015.02.018
  33. Willner P, Hale AS, Argyropoulos S. Dopaminergic mechanism of antidepressant action in depressed patients. Journal of Affective Disorders. 2005;86(1):37-45.  https://doi.org/10.1016/j.jad.2004.12.010
  34. Goldberg JF. Perspectives on the success rate of current antidepressant pharmacotherapy. Expert Opinion on Pharmacotherapy. 2022;23(16):1781-1791. https://doi.org/10.1080/14656566.2022.2138333
  35. Lee MF, Eather R, Best T. Plant-based depressive symptoms in Australian vegans and vegetarians: a cross-sectional study. BMJ Nutrition, Prevention & Health. 2021;4(2):479-486.  https://doi.org/10.1136/bmjnph-2021-000332
  36. Katunina EA. Antioxidant therapy in the complex treatment of Parkinson’s disease. Russkii Meditsinskii Zhurnal. 2010;18(8):468-470. (In Russ.).
  37. Dy AMB, Limjoco LLG, Jamora RDG. Trimetazidine-Induced Parkinsonism: A Systematic Review. Frontiers in Neurology. 2020;11:44.  https://doi.org/10.3389/fneur.2020.00044
  38. Kolesova OE, Ukhanova TYu, Smirnov LD, Shaposhnikova GI, Markin AA. Sposob lecheniya bol’nykh sakharnym diabetom. Patent RF na izobretenie №2134109/10.08.1999. Accessed March 21.03.23. (In Russ.). https://yandex.ru/patents/doc/RU2134109C1_19990810
  39. Volchegorskii IA, Rassokhina LM, Miroshnichenko IY, et al. Effect of pro- and antioxidants on insulin sensitivity and glucose tolerance. Bulletin of Experimental Biology and Medicine. 2010;150(9):295-301. (In Russ.).
  40. Goldstein BJ, Mahadev K, Wu X, et al. Role of insulin-induced reactive oxygen species in the insulin signaling pathway. Antioxidants & Redox Signaling. 2005;7(No. 7-8):1021-1031. https://doi.org/10.1089/ars.2005.7.1021
  41. Volchegorskii IA, Rassokhina LM, Miroshnichenko IYu. Antidepressant action of 3-oxypyridine derivates in mice with alloxan diabetes. Eksperimental’naya i Klinicheskaya Farmakologiya. 2009;72(2):11-15. (In Russ.).
  42. Liua S, Borgland SL. Insulin actions in the mesolimbic dopamine system. Experimental Neurology. 2019;320:113006. https://doi.org/10.1016/j.expneurol.2019.113006
  43. Volchegorskii IA, Miroshnichenko IYu, Rassokhina LM, Faizullin RM. Insulin potentiating and antidepressant effects of 3-oxypyridine and succinic acid derivatives. Eksperimental’naya i Klinicheskaya Farmakologiya. 2014;77(5):6-9. (In Russ.).
  44. Volchegorsky IA, Moskvicheva MG, Chaschina EN. Effects of emoxipine, reamberine and mexidol on neuropathic symptoms and a systolic function of the left ventricular myocardium in patients with diabetes mellitus and diabetic foot syndrome. Terapevticheskii Arkhiv. 2005;77(10):10-15. (In Russ.).
  45. Volchegorsky IA, Mester NV. The influence of 3-oxypyridine antioxidants on depression in patients with diabetes mellitus. Klinicheskaya Meditsina. 2007;85(2):40-45. (In Russ.).
  46. Kolyadich MI, Shaposhnik II. Correction of cardiovascular disorders in diabetic patients with depressive simptoms. CardioSomatika. 2013;4(2):15-19. (In Russ.).
  47. Volchegorsky IA, Rassokhina LM, Miroshnichenko IYu. Antioxidants in experimental diabetes mellitus. Problemy Endokrinologii. 2008;54(5):43-50. (In Russ.).
  48. Volchegorskii IA, Tur EV, Solyannikova OV, et al. Effectiveness of 3-hydroxypyridine and succinic acid derivatives in complex treatment of primary open-angle glaucoma. Eksperimental’naya i Klinicheskaya Farmakologiya. 2012;75(7):20-26. (In Russ.).
  49. Volchegorsky IA, Alekseev MN, Volchegorskaya MI, et al. Effect of a-lipoic acid and mexidol on neuro- and the affective status in patients at early stages of diabetic foot syndrome. Klinicheskaya Meditsina. 2008;86(10):52-59. (In Russ.).
  50. Papanas N, Ziegler D. Efficacy of α-lipoic acid in diabetic neuropathy. Expert Opinion On Pharmacotherapy. 2014;15(18):2721-2731. https://doi.org/10.1517/14656566.2014.972935
  51. Via MA, Chandra H, Araki T, et al. Bromocriptine approved as the first medication to target dopamine activity to improve glycemic control in patients with type 2 diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2010;3:43-48.  https://doi.org/10.2147/DMSO.S9575
  52. Wong ND. Cardiodiabetology: newer pharmacologic strategies for reducing cardiovascular disease risks. Canadian Journal of Physiology and Pharmacology. 2022;100(10):956-967.  https://doi.org/10.1139/cjpp-2022-0065
  53. Volchegorsky IA, Novoselov PN, Astakhova TV. Effect of ascorbic acid and emoxypin on the efficiency of complex chemotherapy for infiltrative pulmonary tuberculosis. Terapevticheskii Arkhiv. 2009;81(11):21-24. (In Russ.).
  54. Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642-1656. https://doi.org/10.1016/S0140-6736(19)30308-3
  55. Volchegorskii IA, Pravdin EV, Pospelova AV, et al. Effect of 3-hydroxypyridine and succinic acid derivatives on bacterial growth in discontinuous cultures. Eksperimental’naya i Klinicheskaya Farmakologiya. 2016;79(4):29-34. (In Russ.). https://doi.org/10.30906/0869-2092-2016-79-4-29-34
  56. Swardfager W, Rosenblat JD, Benlamri M, McIntyre RS. Mapping inflammation onto mood: Inflammatory mediators of anhedonia. Neuroscience and Biobehavioral Reviews. 2016;64:148-166.  https://doi.org/10.1016/j.neubiorev.2016.02.017
  57. Volchegorskii IA, Vazhenin AV, Alekseeva AP. The effect of antioxidant drugs on the self-assessment of clinical symptoms in women during radiation therapy after surgical treatment of endometrial cancer: placebo-controlled randomized trial. Sovremennaya Onkologiya. 2022;24(2):177-183. (In Russ.). https://doi.org/10.26442/18151434.2022.2.201556
  58. Volchegorskii IA, Vazhenin AV, Alekseeva AP. Effect of emoxipine, ethoxidol and mexidol on the quality of life in women during radiotherapy after surgical treatment of endometrial cancer. Eksperimental’naya i Klinicheskaya Farmakologiya. 2022;85(3):25-32. (In Russ.). https://doi.org/10.30906/0869-2092-2022-85-3-25-32
  59. Volchegorskii IA, Sinitskii AI, Miroshnichenko IYu, et al. The effect of 3-hydroxypyridine and succinic acid derivatives on the activity of monoamine oxidases in the brain cortex of rats with alloxan-induced diabetes. Neirokhimiya. 2019;36(3):226-238. (In Russ.). https://doi.org/10.1134/S1027813319020134
  60. Novoselov PN. Economic efficiency of the use of ascorbic acid and emoxypine in the treatment of infiltrative pulmonary tuberculosis. Tuberkulez i Bolezni Legkikh. 2011;88(5):78-79. (In Russ.).
  61. Izarovskii BV. Pharmacoeconomical effectiveness of the use of emoxypine in the complex treatment of alcohol withdrawal syndrome. GlavVrach. 2022;(6)(pril.):89-90. (In Russ.).
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