期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 72, 期 4, 页码 900-909出版社
SPRINGERNATURE
DOI: 10.1007/s12031-021-01964-x
关键词
Parkinson's disease; Amantadine; Tyrosine; 6-Hydroxydopamine; L-DOPA-induced dyskinesia; Acetylcholinesterase
资金
- South-West University of Blagoevgrad, Bulgaria [(sic)H(sic)-01/20.02.2017]
- Institute of Neurobiology, Sofia, Bulgaria
The newly synthesized amantadine derivative Tyr-Am demonstrated significant neuroprotective and antioxidant properties in a 6-OHDA experimental model of Parkinson's disease, comparable to the standard drug amantadine.
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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