Affiliation:
1. Saint-Petersburg State Chemical and Pharmaceutical University; N. P. Behtereva Institute of the Human Brain of the Russian Academy of Sciences
2. Saint-Petersburg State Chemical and Pharmaceutical University
3. Saint-Petersburg State Chemical and Pharmaceutical University; Pavlov Institute of Physiology, Russian Academy of Sciences; Institute of Translational Biomedicine, Saint Petersburg State University; Sirius University of Science and Technology
Abstract
Introduction. α2-adrenergic agonists are not only used as antihypertensive and sedative agents, but are also of interest as potential medications for the treatment of neurological disorders. Previous research has shown a compound from this class, 6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidine-4-ol (mafedine), to exert strong neuroprotection under experimental conditions. Despite its long record of development, the effects of mafedine on animal behavioural characteristics remain unknown.Aim. This work was aimed at evaluating the effects of mafedine sodium at three doses (1, 10, or 50 mg/kg) on white outbred mouse behavior in three tests: Open Field, Elevated Plus Maze, and Light/Dark Box.Materials and methods. Experiments were carried out on 60 white outbred male mice weighing 20–22 g, randomized into 4 groups (n = 15): 1) control (0,9 % saline); 2) mafedine (1 mg/kg); 3) mafedine (10 mg/kg); 4) mafedine (50 mg/kg). All agents were administered via single intraperitoneal injections 20 min before testing. Animal behavior was assessed using the Open Field, Elevated Plus Maze, and Light/Dark Box tests following conventional protocols with group reassignment between tests and an inter-test time interval of at least 2 days. Statistical analysis was carried out using the Prism 8.0.2 software package.Results and discussion. At 1 or 10 mg/kg, mafedine did not affect animal behaviour in either of the tests. At 50 mg/kg, it produced an anxiolytic effect, as indicated by the decrease in the anxiety index values for the Elevated Plus Maze test as well as the increase in peeking out frequency in the Light/Dark Box test, compared to respective control values.Сonclusion. Mafedine sodium salt at doses between 1 and 50 mg/kg was shown to produce no adverse effect on mouse behaviour, indicating a good safety profile of the compound. The discovered anxiolytic effect of mafedine at the highest dose validates its further research not only as a neuroprotector, but also as an anti-anxiety agent.
Publisher
Center of Pharmaceutical Analytics Ltd
Subject
Drug Discovery,Pharmaceutical Science
Reference25 articles.
1. Yuskovets V. N., Chernov N. M., Yakovlev I. P., Okovityi S. V., Sysoev Yu. I., Anisimova N. A. 6-Oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidine-4-olate of sodium and method for preparation thereof. Patent RUS № 2669555 C1. 19.01.2018. Available at: https://patentimages.storage.googleapis.com/19/79/c3/609d6a91fade81/RU2669 Accessed: 08.11.2023. (In Russ.)
2. Sysoev Yu. I., Meshalkina D. A., Petrov D. V., Okovityi S. V., Musienko P. E., Kalueff A. V. Pharmacological screening of a new alpha-2 adrenergic receptor agonist, mafedine, in zebrafish. Neuroscience Letters. 2019;701:234–239. DOI: 10.1016/j.neulet.2019.03.001.
3. Sysoev Y. I., Dagaev S. G., Kubarskaja L. G., Gaikova O. N., Uzuegbunam B. C., Modise K., Makwana T. L., Okovityi S. V. Study of neuroprotective activity of mafedine, an alpha-2 adrenergic receptor agonist, by modeling a traumatic brain injury in rats. Biomedicine. 2019;15(1):62–77. (In Russ.) DOI: 10.33647/2074-5982-15-1-62-77.
4. Sysoev Yu. I., Prikhodko V. A., Chernyakov R. T., Idiyatullin R. D., Musienko P. E., Okovityi S. V. Effects of аlpha-2 аdrenergic аgonist mafedine on brain electrical activity in rats after traumatic brain injury. Brain Sciences. 2021;11(8):981. DOI: 10.3390/brainsci11080981.
5. Sysoev Yu. I., Shustov M. V., Prikhodko V. A., Shits D. D., Puchik M. M., Okovityi S. V. Exploring the molecular and genetic mechanisms of action of the α2-adrenergic agonist mafedine in experimental traumatic brain injury in rats. Russian Journal of Physiology. 2023;109(4):438–456. (In Russ.) DOI: 10.31857/S0869813923040118.