The study of antiparkinsonian activity of the combination of ladasten with fabomotizole in paraquat-induced model of parkinsoian syndrome

Relevance . Parkinson's disease (PD) is a neurodegenerative disease characterized by motor impairments. The currently used antiparkinsonian pharmacotherapy, despite the symptomatic improvement of patients, is associated with severe side effects. The combination of ladasten with fabomotizole may have a potential neuroprotective effect in the neurodegeneration conditions observed in PD, due to its multitargeting action. Objective . The study explores the potential antiparkinsonian activity of a combination of ladasten and fabomotizole in paraquat-induced model of parkinsonian syndrome (PS). Methods . PS was modeled by intraperitoneal administration of paraquat (10 mg/kg) 1 time every 3–4 days for 21 days. The C57Bl/6 mice were divided into 4 groups: 1) passive control, 2) active control, 3) ladasten + fabomotizole combination, 4) levodopa. The animals were tested in the battery of behavioral tests each week of the experiment. Results . The combination of ladasten with fabomotizole successfully treated all manifestations of PS in the battery of behavioral tests, and the greatest difference compared with the active control was found in most tests on the 3rd week of the experiment. Thus, the combination increased latency to fall in the «rotarod test» by 2,38 ( p < 0.0001) and 1.5 times ( p < 0.01) at fixed and accelerating speed, decreased the turning and descent time in the «pole test» by 1.4 ( p < 0.05) and 1.53 times ( p < 0.001). Conclusion . The combination of ladasten with fabomotizole reduced the severity of paraquat-induced PS in the battery of behavioral tests, and it was comparable with the effects of levodopa.