Abstract
The neuroprotective capacity of newly synthesized amantadine derivative tyrosinyl-amantadine (Tyr-Am) with expected antiparkinsonian properties was evaluated in a 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Male Wistar rats were divided into the following groups: sham-operated (SO), striatal 6-OHDA-lesioned control group, 6-OHDA-lesioned rats pretreated for 6 days with Tyr-Am (16 mg/kg administered intraperitoneally, i.p.), and 6-OHDA-lesioned rats pretreated for 6 days with amantadine (40 mg/kg i.p.), used as a referent. On the first, second and third week post-lesion, the animals were subjected to some behavioral tests (apomorphine-induced rotation, rotarod, and passive avoidance test). The acetylcholinesterase (AChE) activity and key oxidative stress parameters including lipid peroxidation levels (LPO) and superoxide dismutase (SOD) were measured in brain homogenates. The results showed that the neuroprotective effect of Tyr-Am was comparable to that of amantadine, improving neuromuscular coordination and learning and memory performance even at a 2.5-fold lower dose. Tyr-Am demonstrated significant antioxidant properties via decreased LPO levels but had no effect on AChE activity. We can conclude that the newly synthesized amantadine derivative Tyr-Am demonstrated significant antiparkinsonian activity in a 6-OHDA experimental model.
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This work was supported by ДHИ-01/20.02.2017 “Preventive effects of new amantadine derivatives against Parkinson’s disease” funded by South-West University of Blagoevgrad, Bulgaria, and the Institute of Neurobiology, Sofia, Bulgaria
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Conception and design [L. Tancheva], [M. Lazarova], [I. Stankova] and [R. Kalfin]. Material preparation, data collection and analysis were performed by [L. Tancheva], [M. Lazarova], [R. Chayrov], [E. Tzvetanova], [A. Alexandrova], [A. Popatanasov], [D. Uzunova] and [M. Stefanova]. The first draft of the manuscript was written by [M. Lazarova] and all authors comment on previous version of the manuscript. All authors read and approved the final manuscript.
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Lazarova, M., Tancheva, L., Chayrov, R. et al. Tyrosinyl-amantadine: A New Amantadine Derivative With an Ameliorative Effect in a 6-OHDA Experimental Model of Parkinson’s Disease in Rats. J Mol Neurosci 72, 900–909 (2022). https://doi.org/10.1007/s12031-021-01964-x
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DOI: https://doi.org/10.1007/s12031-021-01964-x