The translational potential of experimental pharmacology for cerebrovascular disorders

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Abstract

The efficacy of reperfusion therapy to restore cerebral blood supply in patients with ischaemic cerebrovascular disorders is well recognized. Medications with proven cerebrovascular activity, such as oxymethylethylpyridine succinate (Mexidol), nicotinoyl-gamma-aminobutyric acid (Picamilon), and nimodipine, are successfully used in neurological practice with the first two having antiplatelet activity. This review analyses the vascular and antiplatelet effects of those medications, their effect on cerebral blood circulation, blood pressure and the central nervous system, and their neuroprotective activity. Potential compounds are also reviewed: S-amlodipine nicotinate and succinic acid ester of 5-hydroxyadamantan-2-one, which have significant cerebrovascular anti-ischaemic activity but a diametrically opposite effect on blood pressure. S-amlodipine nicotinate lowers blood pressure, while the succinic acid ester of 5-hydroxyadamantan-2-one elevates it. A GABA-positive component is present in the mechanism of action of all the studied drugs except for nimodipine. Experimental data on the effect of substances on cerebral circulation, blood pressure and platelet aggregation, as well as the interaction with GABAA receptors, significantly increase the translational potential of cerebrovascular medications.

About the authors

Ruben S. Mirzoian

Research Zakusov Institute of Pharmacology

Author for correspondence.
Email: cerebropharm@mail.ru
Russian Federation, Moscow

Tamara S. Gan’shina

Research Zakusov Institute of Pharmacology

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Galina A. Kim

Consortium-PIK LLC

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Elena V. Kurza

Research Zakusov Institute of Pharmacology

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Denis V. Maslennikov

Research Zakusov Institute of Pharmacology

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Il'ya N. Kurdyumov

Research Zakusov Institute of Pharmacology

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Antonina I. Turilova

Research Zakusov Institute of Pharmacology

Email: cerebropharm@mail.ru
Russian Federation, Moscow

Aleksander A. Gorbunov

Sechenov First Moscow State Medical University (Sechenov University)

Email: cerebropharm@mail.ru
Russian Federation, Moscow

References

  1. Piradov M.A.,Tanashyan M.M., Maksimova M.Yu. (eds.) [Stroke: modern diagnostic and treatment technologies]. Moscow, 2018; 360 p. (In Russ.)
  2. Benjamin E.J., Munther P., Alonso A. еt al. Heart Disease and Stroke Statistics - 2019 Update: A Report from the American Heart Association. Circulation 2019; 139: e56-e528. doi: 10.1161/CIR.0000000000000659. PMID: 30700139.
  3. Skvortsova V.I., Shetova I.M., Kakorina E.P., Kamkin E.G., Boyko E.L., Dashyan V.G., Krylov V.V. [Healthcare arrangement for patients with stroke in Russia. Results of 10-years implementation of the measures aimed at improvement of medical care for patients with acute cerebrovascular events]. Annals of clinical and experimental neurology 2018; 12(3): 5–12. doi: 10.25692/ACEN.2018.3.1. (In Russ.)
  4. Park J. (ed.). Acute Ischemic Stroke. Acute Ischemic Stroke Medical, Endovascular, and Surgical Techniques. Springer, 2017; 270 p.
  5. Boccardi E., Cenzato M., Curto F. et al. (eds.) Hemorrhagic Stroke. Springer, 2017; 172 p.
  6. Kiris T., Zhang J.H. (eds.) Cerebral vasospasm. New strategies in research and treatment. Springer-Verlag Wien; 2008; 450 p.
  7. Tanashyan M.M., Lagoda O.V., Antonova K.V., Konovalov R.N. [Chronic cerebrovascular diseases and metabolic syndrome: approaches to the pathogenetic treatment of cognitive impairment]. Zhurnal neurologii i psikhiatrii imeni S.S.Korsakova 2016; 9: 106–110. (In Russ.)
  8. Gusev E.I., Chukanova E.I., Chukanova A.S. [Chronic cerebrovascular insufficiency (risk factors, pathogenesis, clinic, treatment)]. Moscow, 2018; 189 p. (In Russ.)
  9. Li Y., Fang W., Tao L. et al. Efficacy and safety of intravenous nimodipine administration for treatment of hypertension in patients with intracerebral hemorrhage. Neuropsychiatr Dis Treat 2015; 11: 1231–1238. doi: 10.2147/NDT.S76882. PMID: 26056454.
  10. Voronina T.A. [Hypoxia and memory. Features of the effects and use of nootropic drugs]. Vestnik RAMN 2000; 9: 27–34. (In Russ.)
  11. Lukyanova L.D., Atabaeva R.E., Shepeleva S.Yu. [Bioenergetic mechanisms of the antihypoxic action of mexidol, the succinate-containing derivative of 3-hydroxypyridine]. Biull Eksp Biol Med 1993; 115: 259–260. PMID: 8054612. (In Russ.)
  12. Kurdyumov I.N., Gan’shina T.S., Maslennikov D.V. et al. [Influence of mexidol and hemisuccinate 2-ethyl-6-methyl-3-hudroxypyridine on cerebral hemodynamics in the hemorrhagic and ischemic damage of the brain]. Eksperimental'naya i klinicheskaya farmakologiya 2019; 82(2): 3–6. (In Russ.)
  13. Mirzoyan R.S., Gan’shina T.S., Khailov N.A. et al. [Cerebrovascular pharmacology of separate and combined vascular pathology of brain and heart]. Eksperimental'naya i klinicheskaya farmakologiya 2014; 77(3): 3–12. (In Russ.)
  14. Gnezdilova A.V., Gan’shina T.A., Mirzoyan R.S. [GABAergic mechanism of cerebrovascular effet of mexidol]. Eksperimental'naya i klinicheskaya farmakologiya 2010; 73(10): 11–13. (In Russ.)
  15. Tanashyan M.M., Lagoda O.V., Antonova K.V. [Chronic cerebrovascular diseases on the background of the metabolic syndrome: new approaches to treatment]. Zhurnal nevrologii i psikhiatrii im. C.C. Korsakova 2012; (11): 21–26. (In Russ.)
  16. Mirzoyan R.S., Gan’shina T.S. [The new cerebrovascular preparation pikamilon]. Farmakol Toksikol 1989; 52(1): 23–26. PMID: 2707413. (In Russ.)
  17. Mirzoian R.S., Gan’shina Т.S., Kosoi M.Iu. et al. [Effect of pikamilon on the cortical blood supply and microcirculation in the pial arteriole system]. Biull Eksp Biol Med 1989; 107: 581–582. PMID: 2736292. (In Russ.)
  18. Bendikov E.A., Shmuylovich L.M., Kopelevich V.M. [Effect of gamma-aminobutyric acid, nicotinoyl-gamma-aminobutyric acid and its ethyl ester on central processes of formation of vasomotor reflexes] Biull Eksp Biol Med 1972; 73: 65–69. PMID: 5011195. (In Russ.)
  19. Silkina I.V., Gan’shina 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.)
  20. Kovalev G.I., Vasilyeva E.V., Salimov R.M. [The effect of picamilon on the GABA receptors of the prefrontal cortex and the behavior of C57BL/6 and BALB/c mice in a closed cruciform labyrinth]. Eksperimental'naya i klinicheskaya farmakologiya 2017; 80(3): 3–9. (In Russ.)
  21. Scriabine A.,van den Kerckhoff W. Pharmacology of nimodipine. A review. Ann N Y Acad Sci 1988; 522: 698–706. doi: 10.1111/j.1749-6632.1988.tb33415.x. PMID: 3288065.
  22. Towart R., Perzborn E. Nimodipine inhibits carbocyclic thromboxane-induced contractions of cerebral arteries. Eur J Pharmacol 1989; 69: 213–215. doi: 10.1016/0014-2999(81)90417-9. PMID: 7202520.
  23. Hänggi D., Turowski B., Perrin J. et al. The effect of an intracisternal numodipine slow-release system on cerebral vasospasm after experimental subarachnoid hemorrhage in the rat. Acta Neurochi 2008; 104(Suppl): 103–107.
  24. Mirzoyan R.S., Gan’shinaТ.S., Kim G.A. et al. [Differences between cerebrovascular effects of 5-hydroxyadamantane-2-one, nimodipine and S-amlodipine nicotinate in the hemorrhagic and ischemic model damage of rat brain]. Eksperimental'naya i klinicheskaya farmakologiya 2018; 81(5): 3–6. doi: 10.30906/0869-2092-2018-81-5-3-6. (In Russ.)
  25. Mirzoyan R.S., Gan'shina Т.S., Kim G.A. et al. [Pharmacological correction of cerebrovascuklar disordes in various experimental pathological conditions]. Annals of clinical and experimental neurology 2018; 12(1): 31–37. doi: 10.25692/ACEN.2018.1.5. (In Russ.)
  26. 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.)
  27. Pisani A., Calabresi P., Tozzi A. et al. L-type Ca2+ channel blockers attenuate electrical changes and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons. Stroke 1998; 29: 196–201. PMID: 9445351.
  28. Tomassoni D., Lanari A., Silvestrelli G. et al. Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens 2008; 30: 744–766. doi: 10.1080/10641960802580232. PMID: 19021025.
  29. Hockel K., Diedler J., Steiner J. et al. Effect of intra-arterial and intravenous nimodipine therapy of cerebral vasospasm after subarachnoid hemorrhage on cerebrovascular reactivity and oxygenation. World Neurosurg 2017; 101: 372–378. doi: 10.1016/j.wneu.2017.02.014. PMID: 28232152.
  30. Kim S.A., Park S., Chung N. et al. Efficacy and safety profiles of a new S(-)-amlodipine nicotinate formulation versus racemic amlodipine besylate in adult Korean patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, noninferiority clinical trial. Clin Ther 2008; 30: 845–857. doi: 10.1016/j.clinthera.2008.05.013. PMID: 18555932.
  31. Gan’shina T.S., Kim G.A, Gnezdilova A.V. et al. [Comparative study of the effect of S-anlodipine nicotinate and amlodipine besylate on the arterial pressure of awake rats]. Eksp Klin Farmakol 2014; 77(8): 20–22. PMID: 25335386. (In Russ.)
  32. Kurza E.V., Avdyunina N.I., Gan’shina T.S. et al. [Synthesis and cerebrovascular anti-ishemic activity of new 5-hydroxyadamantan-2-one derivates]. Khimiko-farmatsevticheskiy zhurnal 2018; 52(2): 3–7. (In Russ.)
  33. Tanashyan M.M., Shabalina A.A., Gnedovskaya E.V. et al. [Antiplatelet and anti-ischemic effects of memantine and 5-hydroxyadmantan-2-one in patients with cerebrovascular disease and in experiment]. Eksp Klin Farmakol 2016; 79(2): 20–23. PMID: 27416678.
  34. Krause D.N., Wong E., Degener P., Roberts E. GABA receptors in bovine cerebral blood vessels: binding studies with [3H]muscimol. Brain Res 1980; 185: 51–57. doi: 10.1016/0006-8993(80)90669-1. PMID: 6243504.
  35. Napoleone P., Erdo S., Amenta F. Autoradiographic localization of the GABAA- receptor agonist [3H]muscimol in rat cerebral vessels. Brain Res 1987; 423: 109–115. doi: 10.1016/0006-8993(87)90830-4. PMID: 2823981.
  36. Napoleone P., Ferrante F., Amenta F. Evidence against the existence of GABAB receptor sites in rat cerebrovascular tree. Pharmacol Res 1990; 22: 337–342. PMID: 2164190.
  37. Mirzoyan R.S., Gan’shinaТ.S., Gorbunov A.A. et al. [Pharmacology of various neuromediator mechanisms of regulation of cerebral circulation]. Eksp Klin Farmakol 2017; 80(9): 35–39.

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Copyright (c) 2019 Mirzoian R.S., Gan’shina T.S., Kim G.A., Kurza E.V., Maslennikov D.V., Kurdyumov I.N., Turilova A.I., Gorbunov A.A.

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