Experimental research of cerebroprotective activity of the new 4-aminobutatanoic acid derivative

Keywords: new derivative of 4-aminobutanoic acid, acute cerebrovascular accident in rats, cerebroprotective activity

Abstract

The aim. To study the cerebroprotective activity of a new derivative of 4-aminobutanoic acid the compound KGM-5 on the effect on survival and behavioural responses, cognitive impairment and neurological deficits in rats with acute cerebrovascular accident.

Materials and methods. Acute cerebrovascular accident (ACVA) was simulated in rats by irreversible unilateral carotid occlusion (UCO) under anesthesia with sodium thiopental (35 mg/kg, intraperitoneally, IP). Five groups of animals were used: intact control (IC, n=6), a group of animals with ACVA, which were not treated (control pathology, CP, n=13); group of animals with ACVA, which were treated for 5 days after surgery (first injection 30 min before surgery) with the compound KGM-5 (ACVA+KGM-5, n=14) at a conditionally effective dose of 30 mg/kg body weight of animals, a group of animals with ACVA (ACVA+CD “Picamilon”, n=13), who received IP for 5 days, the comparison drug (CD) “Picamilon” at a dose of 17 mg/kg and pseudo-operated animals (POA), n=8), which were operated without ligation of the carotid artery, which allows to level the effect of anesthesia and surgery on the studied indicators. The cerebroprotective effect of the studied agents was assessed by an integral criterion – survival of animals (throughout the experiment), indicators of neurological deficit (24, 48, 72, 94 hours after ACVA modelling), the state of cognitive functions in the test of extrapolation escape test (EET) (72 hours after ACVA modelling)

Results. The KGM-5 compound contributed to a significant reduction in the severity of neurological deficit, as evidenced by significant differences in this indicator compared with CP, respectively, the first (0.5 points vs. 1.25 points, p<0.05), the third (0.0 points against 1.0 point, p<0.05) and the fourth day (0.0 points vs. 0.5 points, p<0.05) after OCO. Under the influence of CD “Picamilon” reduction of neurological deficit compared with CP was observed on the first, third and fourth days, but these differences were insignificant (p>0.05). Both studied agents - the compound KGM-5 and CD “Picamilon” contributed to the improvement of cognitive functions of rats with ACVA, as evidenced by a significant reduction (p<0.05) of the latent period of diving in the EET, respectively, 1.8 and 1.7 times compared with CP and did not show a significant effect on animal survival.

Conclusion. The cerebroprotective activity of a new 4-aminobutanoic acid derivative in the conditions of acute cerebrovascular accident in rats was established in terms of the ability to reduce the severity of neurological deficits and improve cognitive functions in the extrapolation escape test. The severity of cerebroprotective activity of the new compound is not inferior to GABA-ergic drug “Picamilon”.

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Author Biographies

Oksana Mishchenko, National University of Pharmacy

Department of Clinical Pharmacology

Natalia Palagina, National University of Pharmacy

Department of Clinical Pharmacology

References

Kamchatnov, P. R., Umarova, Kh. Ya., Chugunov, A. V. (2015). Management of patients with cognitive impairment. Nervous Diseases, 4, 18–22.

Kovalchuk, V. V. (2020). Cognitive dysfunction. Modern view of etiopathogenesis, diagnosis and therapy. Effective pharmacotherapy, 16 (31), 40–52.

Kuznetsova, S. M., Mankovsky, N. B. (2013). Age-related changes in neurotransmitter systems of the brain as a risk factor for cerebrovascular pathology. Journal of Neurology B. N. Mankowski, 2, 5–13.

Surawan, J., Areemit, S., Tiamkao, S., Sirithanawuthichai, T., Saensak, S. (2017). Risk factors associated with post-stroke dementia: a systematic review and meta-analysis. Neurology International, 9 (3). doi: http://doi.org/10.4081/ni.2017.7216

Sahathevan, R., Brodtmann, A., Donnan, G. A. (2011). Dementia, Stroke, and Vascular Risk Factors; a Review. International Journal of Stroke, 7 (1), 61–73. doi: http://doi.org/10.1111/j.1747-4949.2011.00731.x

Kovalchuk, V. V., Barantsevich, E. R. (2017). Chronic cerebral ischemia. A modern view on etiology, diagnostics and therapy. Effective pharmacotherapy, 19, 26–32.

Fedin, A. I. (2014). Selected Lectures on Outpatient Neurology. Moscow: AST 345, 128.

Mufson, E. J., Binder, L., Counts, S. E., DeKosky, S. T., deToledo-Morrell, L., Ginsberg, S. D. et. al. (2012). Mild cognitive impairment: pathology and mechanisms. Acta Neuropathologica, 123 (1), 13–30. doi: http://doi.org/10.1007/s00401-011-0884-1

Belskaya, G. N., Chuprina, S. E., Vorobyev, A. A., Gorozha, E. N., Butorakina, T. L., Sokolov, M. A., Izmaylov, I. A. (2016). Cognitive disorders in stroke patients: the possibilities of pharma­cological correction. Zhurnal Nevrologii i Psikhiatrii Im. S.S. Korsakova, 116 (5), 33–37. doi: http://doi.org/10.17116/jnevro20161165133-37

Mishchenko, T. S., Zdesenko, I. V., Linskaya, A. V., Mishchenko, V. N. (2011). New targets for therapeutical impact in patients with chronic brain ischemia. International Journal of Neurology, 2 (40), 7–13.

Morozova, O. G. (2013). Nootropics in the complex therapy of chronic cerebral ischemia: mechanisms of action and therapeutic possibilities of pramiracetam. International Journal of Neurology, 5 (59), 143–148.

Yevtushenko, E. S. (2013). Nootropics and neuroprotectors in modern clinical neuropharmacology. International Journal of Neurology, 3 (57), 20–27.

Mishchenko, O. Ya., Golik, M. Yu., Hrytsenko, I. S. Komisarenko A. M., Palahina, N. Yu., Mishchenko, M. V. (2017). Pat. No. 120512 UA. Application of 4-aminobutanoic acid derivatives as antiamnestic agents. MPK: A61K 31/197 (2006.01), A61P 25/00. No. u201703627; declareted: 13.04.2017; published: 10.11.2017, No. 21.

Preclinical study of the specific activity of potential drugs of primary and secondary neuroprotection (2016). Kyiv: LLC "Yuston Publishing House", 80.

Pro zatverdzhennia Poriadku provedennia doklinichnoho vyvchennia likarskykh zasobiv (2009). Nakaz MOZ Ukrainy No. 944. 14.12.2009. Available at: https://zakon.rada.gov.ua/laws/show/z0053-10#Text

Mironov, A. N. (Ed.) (2012). Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyih sredstv. Moscow: Grif i K, 944.

Deiko, R. D., Shtrygol, S. Yu., Kolobov, A. A., Mishchenko, O. Ya. (2015). The correction of neurological and cognitive disorders on the model of cerebral ischemia using original neuroactive oligopeptides. Pharmacology and drug toxicology, 1 (42), 24–29.

Petri, A., Sabin, K. (2015). Visual medical statistics. Moscow: GEOTAR-Media, 216.

Gantsgorn, E. V., Khloponin, D. P., Maklyakov, Yu. S. (2013). Pathophysiological basics of acute brain ischemia modern pharmacotherapy. Nootropics and antioxidants’ role in neuroprotection. Medical Herald of the South of Russia, 2, 4–12.

Burchynskyi, S. H. (2015). GABA-ergic agents in the pharmacotherapy of chronic cerebral ischemia. International Neurologic Journal, 1 (71), 101–105.


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Published
2021-05-25
How to Cite
Mishchenko, O., & Palagina, N. (2021). Experimental research of cerebroprotective activity of the new 4-aminobutatanoic acid derivative. EUREKA: Health Sciences, (3), 95-100. https://doi.org/10.21303/2504-5679.2021.001851
Section
Pharmacology, Toxicology and Pharmaceutical Science