Advances in neurometabolic therapy
Abstract
Actovegin is a calf blood extract that contains more than 200 biologically active compounds. Experiments have shown that Actovegin reduces the neurotoxic effect of amyloid, neutralizes reactive oxygen species, and normalizes the endothelial function of small vessels. The drug has not been shown to stimulate tumor growth in the neuroblastoma model. Clinical experience with Actovegin suggests that the drug has an undoubted efficacy in treating moderate vascular cognitive impairment and chronic distal symmetric diabetic polyneuropathy and that it is used as additional therapy for primary degenerative and vascular dementia. The clinical efficacy of Actovegin in chronic obliterating diseases of the lowerlimb arteries is being actively studied now.
About the Authors
V. V. Zakharov
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation
Russian Federation
Department of Nervous System Diseases and Neurosurgery,
11, Rossolimo St., Build 1, Moscow 119021
N. V. Vakhnina
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation
Russian Federation
Department of Nervous System Diseases and Neurosurgery,
11, Rossolimo St., Build 1, Moscow 119021
References
1. Buchmayer F, Pleiner J, Elminger MW, et al. Actovegin®: a biological drug for more than 5 decades. Wien Med Wochenschr. 2011;161 (3-4):80-8. doi: 10.1007/s10354-011-0865-y
2. Machicao F, Muresanu DF, Hundsberger H, Pflü ger M, Guekht A. Pleiotropic neuroprotective and metabolic effects of Actovegin's mode of action. J Neurol Sci. 2012;322(1):222-7. doi: 10.1016/j.jns.2012.07.069
3. Herrschaft H, Kunze U, Gleim F. The action of Actovegin on cerebral blood flow and cerebral metabolism in man. Med Welt. 1977;28:339-45.
4. Jager KH, Leybold K, Mittenzwei H, et al. The promotional of cell respiration by a blood extract. Arzneimittel-Forschung / Drug Res. 1965; 15:750-4.
5. De Groot, Brecht M, Machicao F. Evidence for a factor protective against hypoxic liver parenchymal cell injury in a protein-free blood extract. Res Comm Chem Path Pharm. 1990; 68:125-8.
6. Reichel H, Weiss C, Leichtweiss HP. The effects of a blood extract on the oxygen uptake of isolated artificially perfused kidneys and skeletal muscles in rats. Arzneim-Forsch. 1965;15(756):757.
7. Kuninaka T, Senga Y, Senga H, Weiner M. Nature of enhanced mitochondrial oxidative metabolism by a calf blood extract. J Cell Physiol. 1991;146(1):148-55. doi: 10.1002/jcp.1041460119
8. Bachmann W, Forster H, Mehnert H. Experimental studies in animals on the effect of a protein-free blood extract on the metabolism of glucose. Arzneimittel-Forschung / Drug Res. 1968;18:1023-7.
9. Parade D, Biro G, Ketti H, et al. Studies on the insulin-like action of a low molecularweight blood extract on the glucose metabolism of isolated isolated tissue of the rat in vitro. Arzneimittel-Forschung / Drug Res. 1968;18: 1019-21.
10. Mohnike G, Lippmann HG, Dieckmann I, et al. Zur Wirkung eines Extraktes aus Kalberblut im Stoffwechsel der Glucose. Arzneimittel-Forschung / Drug Res. 1968;18:1021.
11. Machicao F, Mü hlbacher Ch, Haring HU. Inositol phospho-ooligosaccharides from a dialysate [Actovegin] obtained from blood mimic the effect on lipogenesis glucose transport and lipolysis in rat adipocytes. Aktuelle Endokrinologie und Stoffwechsel. 1989;10(2):111.
12. Machicao F, Sixt B, Seffer E, et al. Adipocytes release inositol phosphate oligosaccharides with insulin like activity similarly as found in hemodialysate. In: IV International Symposium on Insulin Receptor and Insulin Action, Verona, Italy; 1990. P. 124.
13. Machicao F, Mushack J, Seffer E, et al. Mannose, glucosamine and inositol monophosphate inhibit the effects of insulin on lipogenesis. Further evidence for a role for inositol phosphate-oligosaccharides in insulin action. Biochem J. 1990;266:909-16.
14. Jaacob S, Dietze GJ, Machicao F, et al. Improvement of glucose metabolism in patients with type II diabetes after treatment with hemodialysate. Arzneimittelforschung. 1996;(3): 269-72.
15. Dieckmann A, Kriebel M, Andriambeloson E, et al. Treatment with Actovegin improves sensory nerve function and pathology in streptozotocin-diabetic rats via mechanisms involving inhibition of PARP activation. Exp Clin Endocrinol Diabetes. 2011;120(3):132-8.
16. Elmlinger MW, Kriebel M, Ziegler D. Neuroprotective and Anti-Oxidative Effects of the Hemodialysate Actovegin on Primary Rat Neurons in Vitro. Neuromolecular Med. 2011; 13(4):266-74. doi: 10.1007/s12017-011-8157-7
17. Fedorovich AA. Non-invasive evaluation of vasomotor and metabolic functions of microvascular endothelium in human skin. Microvasc Res. 2012;84:86-93. doi: 10.1016/j.mvr.2012.03.011
18. Meilin S, Machicao F, Elmlinger M. Treatment with Actovegin improves spatial learning and memory in rats following transient forebrain ischaemia. J Cell Mol Med. 2014;18(8): 1623-30. doi: 10.1111/jcmm.12297
19. Herrmann WM, Bohn-Olszewsky WJ, Kuntz G. Actovegin infusion treatment in patients with primarily degenerative dementia of the Alzheimer type and multi-infarct dementia. Zeitschrift fü r Geriatrie. 1992;5:46-55. 20. Kanowski S, Kinzler E, Lehmann E, et al. Confirmed Clinical Efficacy of Actoveginmin Elderly Patients with Organic Brain Syndrome. Pharmacopsychiat. 1995;28:125-33. doi: 10.1055/s-2007-979604
20. Guekht A, Skoog I, Edmundson S, et al. ARTEMIDA trial (A Randomized Trial of Efficacy, 12 Months International DoubleBlind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment. Stroke. 2017;48:1262-70. doi: 10.1161/STROKEAHA.116.014321
21. Yannsen V, Brukner GV. Treatment of chronic cerebrovascular insufficiency using actotegin forte pills. Russkii Meditsinskii Zhurnal. 2002;10(12):1-4 (In Russ.).
22. Oswald WD, Steiger W, Oswald B, Kuntz G. Die Verbesserung fluider kognitiver leistungen als indikator fuer die klinische Wirksamkeit einer nootropen Substanz. Eine Placebo-kontrollierte Doppelblind-Studie mit Actovegin). Zeitschrifft fur Gerontopsychologie und Psychiatrie. 1991;4:209-20.
23. Saletu B, Gruenberg J, Linzmayer L, et al. EEG Brain Mapping and Psychometry in AgeAssociated Memory Impairment after Acute and 2-Week Infusions with the Gemoderivative Actovegin: Double-Blind, Placebo-Controlled Trials. Neuropsychobiology. 1990;91(24):135-48. doi: 10.1159/000119476
24. Saletu B, Griinberger I, Linzmayer L, Stahr H. Zur Funktionsverbesserung des alternden Gehirns: Plazebokontrollierte PharmaltoEEG und psychometrische Studien mit einem stoffwechselaktiven Hamoderivat (Actovegin). Gerontol. 1984;17:271-9.
25. Semiitsch HV, Anderer P, Saletu B, Hochmayer I. Topographic mapping of cognitive event-related potentials in a double-blind, placebo-controlled study with the hemoderivative Actovegin in age-associated memory impairment. Neuropsychobiology. 1990-1991; 24:49-56. doi: 10.1159/000119042
26. Fedorovich AA, Soboleva GN. Correction of cognitive impairment with Actovegin in patients with arterial hypertension and coronary heart disease. Effektivnaya Farmakoterapiya. 2015; 23:42-51 (In Russ.).
27. Mikhailova NM, Selezneva ND, Kalyn YaB, et al. Efficacy of treatment with aktovegin elderly patients with mild cognitive decline syndrome of vascular genesis. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2013; 7(2):68-75 (In Russ.).
28. Ostroumova OD. Correction of cognitive impairment with Actovegin in patients with essential hypertension. Meditsinskii Alfavit. 2012;(4):4-8 (In Russ.).
29. Zakharov VV, Sosina VB. Possibilities of antihypoxic drugs in the treatment of moderate cognitive impairment in patients with diabetes mellitus. Lechashchii Vrach. 2010;(3):87-91 (In Russ.).
30. Ziegler D, Movsesyan L, Mankovsky B, et al. Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes Care. 2009;32(8):1479-84. doi: 10.2337/dc09- 0545
31. Morgoeva FE, Ametov AS, Strokov IA. Diabetic encephalopathy and polyneuropathy: Actovegin's therapeutic potential. Russkii Meditsinskii Zhurnal. 2005;(6): 302-6 (In Russ.).
32. Horsch S, Claeys L, Diehm C, et al. [Assessment of the clinical effectiveness of actihaemyl in Fontaine stage IIb intermittent claudication]. Vasa Suppl. 1992;37:64-5.
33. Angelkort B, Ruhlmann KU, de la Haye R, et al. Influence of deproteinized hemodialysate on rest pain and walking distance in the presence of peripheral chronic arterial occlusive disease. Angiology. 1992;43:47-58. doi: 10.1177/000331979204300106
34. Uchkin IG, Zudin AM, Bagdasaryan AG, Fedorovich AA. The effect of pharmacotherapy of chronic obliterating diseases of lower limb arteries on the state of the microvasculature. Angiologiya i Sosudistaya Khirurgiya. 2014; 20(2):27-36 (In Russ.).
35. Stein R, Seuser J. Local use of Actovegin ampoule solution in crural ulcer. Med Welt. 1986;37:173-6.
36. Uchkin IG, Mosesov AG, Tsyrul'nikov AA. Actovegin as a component of the complex therapy of complicated forms of chronic venous insufficiency of the lower extremities. Russkii Meditsinskii Zhurnal. 2007; 12(15):981-5 (In Russ.).
37. Khismatov RR, Trukhova VV, Makarova NN, Guseva SL. Actovegin in the treatment of trophic ulcers of the lower extremities of venous etiology. Russkii Meditsinskii Zhurnal. 2008;30(16):2022-4 (In Russ.).
38. https://clinicaltrials.gov/ct2/show/NCT03469349?term=Actovegin&rank=1
39. Sondergard SD, Dela F, Helge JW, Larsen S. Actovegin, a nonprohibited drug increases oxidative capacity in human skeletal muscle. Eur J Sport Sci. 2016;16:801-7. doi: 10.1080/17461391.2015.1130750
40. Lee P, Rattenberry A, Connelly S, Nokes L. Our experience on Actovegin, is it cutting edge? Int J Sports Med. 2011;32:237-41. doi: 10.1055/s-0030-1269862
41. WADA. Список запрещенных препаратов (2017 г.). Доступно по ссылке: https://www.wadaama.org/en/media/news/201 6-09/wadapublishes-2017-prohibited-list [WADA, List of prohibited drugs (2017). Available by reference: https://www.wadaama.org/en/media/news/201 6-09/wadapublishes-2017-prohibited-list].
42. Reichl FY, Holdt LM, Teupser D, et al. Comprehensive analytics of Actovegin® and its effect on muscle cells. Int J Sports Med. 2017; 38:809-18. doi: 10.1055/s-0043-115738
43. Pforringer W, Pfister A, Kuntz G. The treatment of Achilles paratendinitis: results of a double-blind, placebo-controlled study with a deproteinized hemodialysate. Clin J Sport Med. 1994;4:92-9. doi: 10.1097/00042752-199404000-00005
44. Boichenko MN, Volchkova EV, Pak SG. Biopreparations and prion diseases, is etiological connection possible? Farmateka. 2012;s3-12:47-54 (In Russ.).
45. Vinokurov MG, Yurinskaya MM, Knyazev AV, Astashkin EI. Effect of calf blood hemoderivate on viability, apoptosis and necrosis of human neuroblastoma cells SK-N-SH. Eksperimental'naya i Klinicheskaya Farmakologiya. 2017; 80(3):31-5 (In Russ.).
Review
For citations:
Zakharov V.V., Vakhnina N.V. Advances in neurometabolic therapy. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3):129-136. (In Russ.) https://doi.org/10.14412/2074-2711-2019-3-129-136
Views: 424
Email this article 