Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental Neurology2075-54732409-2533Research Center of Neurology68410.25692/ACEN.2020.3.7UnknownExpanding the horizons of antiplatelet therapy. A pilot study of the antiplatelet properties of a new tropane alkaloidMirzoianRuben S.cerebropharm@mail.ruShabalinaAlla A.cerebropharm@mail.ruGan’shinaTamara S.cerebropharm@mail.ruKurdyumovIl'ya N.cerebropharm@mail.ruTurilovaAntonina I.cerebropharm@mail.ruKostochkaLeonid M.cerebropharm@mail.ruKozlovAnton V.cerebropharm@mail.ruAnnushkinVladislav A.cerebropharm@mail.ruKornilovaAnastasia A.cerebropharm@mail.ruTanashyanMarine M.cerebropharm@mail.ruResearch Zakusov Institute of PharmacologyResearch Center of Neurology14092020143535914092020Copyright © 2020, Mirzoian R.S., Shabalina A.A., Gan’shina T.S., Kurdyumov I.N., Turilova A.I., Kostochka L.M., Kozlov A.V., Annushkin V.A., Kornilova A.A., Tanashyan M.M.2020<p><strong>Introduction.</strong><span class="s31">The article discusses the search for new and highly effective drugs for the prevention and treatment of cerebrovascular disease. The</span><strong>aim</strong><span class="s31">was to examine the effect of the acyl hydrazone tropane derivative on individual platelet aggregation (PA) sensitivity in in vitro studies.</span></p>
<p><span class="s31"><strong>Results</strong>. We present the results of a pilot study on the effect of a new acyl hydrazone tropane derivative acyl hydrazone (2,3,4-trimethoxy-N'-(8-methyl-8-azabicyclo [3.2.1.] octane-3-ylidene) benzohydrazide hydrochloride on PA properties in vitro in healthy volunteers and in patients with chronic cerebrovascular disease. </span></p>
<p><span class="s31"><strong>Conclusion</strong>. The studied compound has a pronounced ability to suppress PA when administered intravenously in vivo in two concentrations, equivalent to doses of 10 and 100 mg/kg, and its effect is superior to the comparator acetylsalicylic acid, which is used in clinical practice as an antiplatelet drug.</span></p>cerebrovascular diseasetropane acyl hydrazone derivativeplatelet aggregationacetylsalicylic acidцереброваскулярные заболеванияпроизводное ацилгидразона тропанаагрегация тромбоцитов, ацетилсалициловая кислота[Piradov M.A., Tanashyan M.M., Maksimova M.Yu. (eds.) [Stroke: modern diagnostic and treatment technologies: a guide for doctors]. Moscow, 2018. 360 p. DOI: 10.24421/MP.2018.18.15909. (In Russ.)][Tanashyan M.M., Domashenko M.A., Raskurazhev A.A. [Aspirin resistance: clinical and molecular genetic assessment methods]. Annals of Clinical and Experimental Neurology 2016; 10(1): 41–46. (In Russ.)][Mirzoyan R.S., Naplekova P.L., Ganshina T.S. et al. [New anti-migraine agent with antiserotonin, cerebrovascular and anxiolytic activity]. Eksperimental’naya i klinicheskaya farmakologiya 2017; 80(4): 8–12. (In Russ.)][Gryglas A., Smigiel R. Migraine and stroke: What’s the link? What to do? Curr Neurol Neurosci Rep 2017; 17: 22. DOI: 10.1007/s11910-017-0729-y. PMID: 28283957.][Kruit M.C. van Buchem M.A., Launer L.J. et al. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study. Cephalalgia 2010; 30: 129–136. DOI: 10.1111/j.1468-2982.2009.01904.x. PMID: 19515125.][Zhang S., Zhang W., Zhou G. Extended risk factors for stroke prevention. J Natl Med Assoc 2019; 111: 447–456. DOI: 10.1016/j.jnma.2019.02.004. PMID: 30878142.][Li L., Schulz U.G., Kuker W., Rothwell P.M. Age-specific association of mi- graine with cryptogenic TIA and stroke: population-based study. Neurology 2015; 85: 1444–1451. DOI: 10.1212/WNL.0000000000002059. PMID: 26423431.][Vasiliev S.A., Melkumyan A.L., Berkovsky A.L. et al. [Clinical and laboratory diagnostics of platelet dysfunction]. Moscow, 2013. 76 p. (In Russ.)][Born G.V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927–929. DOI: 10.1038/194927b0. PMID: 13871375.][Mawet J., Kurth T., Ayata C. Migraine and stroke: in search of shared mechanisms. Cephalalgia 2015; 35: 165–181. DOI: 10.1177/0333102414550106. PMID: 25228681.][Tietjen G.E., Herial N.A., White L. et al. Migraine and biomarkers of endo- thelial activation in young women. Stroke 2009; 40: 2977–2982. DOI: 10.1161/ STROKEAHA.109.547901. PMID: 19608996.][Dressman J.B., Nair A., Abrahamsson B. et al. Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid. J Pharm Sci 2012; 101: 2653–2667. DOI: 10.1002/jps.23212. PMID: 22674043.][Tanashyan M.M., Shabalina A.A., Lagoda O.V. et al. [Multimodal approach to the correction of neurological manifestations of chronic cerebral ischemia]. Terapevticheskiy arkhiv 2018; 90(12): 61–67. DOI: 10.26442/00403660.2018.12. 000010. (In Russ.)][Piradov M.A., Maksimova M.Yu., Tanashyan M.M. (eds.) [Stroke: step-bystep instructions]. Мoscow, 2019. 272 p. URL: https://www.rosmedlib.ru/book/ ISBN9785970449103 (In Russ.)][Vasilieva T.M., Petrukhina G.N., Miftakhova N.T. et al. [The action of the anti-migraine drug antagonist of serotonin receptors tropoxin on platelet aggregation]. Eksperimental’naya i klinicheskaya farmakologiya 2005; 68(3): 30–33. (In Russ.)][Bousser M.-G., Amarenco P., Chamorro A. et al. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet 2011; 377: 2013–2022. DOI: 10.1016/ S0140-6736(11)60600-4. PMID: 21616527.][Mirzoyan R.S., Ganshina T.S., Kim G.A. et al. [Translational potential of experimental pharmacology of cerebrovascular disorders]. Annals of Clinical and Experimental Neurology 2019; 13(3): 34–40. DOI: 10.25692/ACEN.2019.3.5. (In Russ.)][Krasnikov A.V., Abaimov D.A., Noskova T.Yu. et al. [The use of drug monitoring of topiramate for the individualization of preventive anti-migraine therapy]. Eksperimental’naya i klinicheskaya farmakologiya 2018; 81(7): 20–24. DOI: 10.30906/0869-2092-2018-81-7-20-24. (In Russ.)][Rau J.C., Dodick D.W. Other preventive anti-migraine treatments: ACE inhibitors, ARBs, calcium channel blockers, serotonin antagonists, and NMDA receptor antagonists. Curr Treat Options Neurol 2019; 21: 17. DOI: 10.1007/ s11940-019-0559-0. PMID: 30880363.][Osipova V.V., Filatova E.G., Artemenko A.R. et al. [Diagnostics and treatment of migraine: recommendations of Russian experts]. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova 2017; 117(1): 28–42. DOI: 10.17116/jnevro20171171228-42. (In Russ.)][Fozard J.R., Kalkman H.O. 5-Hydroxytryptamine (5-HT) and the initiation of migraine: new perspectives. Naunyn Schmiedebergs Arch Pharmacol 1994; 350: 225–229. DOI: 10.1007/BF00175026. PMID: 7824037.][Romanycheva A.N., Ganshina T.S., Mirzoyan R.S. [Individual sensitivity to the cerebrovascular antiserotonin action of propranolol and tolfenamic acid]. Eksperimental’naya i klinicheskaya farmakologiya 1995; 58(2): 25–26. (In Russ.)][Ganshina T.S. [Neurotransmitter mechanism of action of tropoxin in com parison with anti-migraine drugs]. Eksperimental’naya i klinicheskaya farmakologiya 2003; 66(3): 17–20. (In Russ.)]