Clinical and Experimental Neuroscience (NiCE), Institute for Aging Research, School of Medicine, Campus Mare Nostrum, The European University for Well-Being, EUniWell, University of Murcia, Spain.
Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Campus of Health Sciences, University of Murcia, 30120 Murcia, Spain.
Open Biol. 2023 May;13(5):220370. doi: 10.1098/rsob.220370. Epub 2023 May 17.
Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3-4 months until they developed LIDs. Three animals were then co-treated with a single dose of 7-NI administered 45 min before each L-DOPA treatment. Dyskinetic MPTP-treated monkeys showed a significant decrease in LIDs compared with their scores without 7-NI treatment ( < 0.05). The anti-Parkinsonian effect of L-DOPA was similar in all three monkeys with and without 7-NI co-treatment. This improvement was significant with respect to the intensity and duration of LIDs while the beneficial effect of L-DOPA treatment was maintained and could represent a promising therapy to improve the quality of life of PD patients.
一氧化氮（NO）在整合基底神经节中的多巴胺传递方面起着关键作用，并与帕金森病（PD）的发病机制有关。本研究的目的是确定一氧化氮合酶抑制剂 7-硝基吲唑（7-NI）是否能够减少慢性 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）中毒的 PD 非人类灵长类动物模型中的 L-多巴诱导的运动障碍（LIDs）。六只帕金森病猴每天接受 L-多巴治疗 3-4 个月，直到出现 LIDs。然后，其中 3 只动物在每次 L-DOPA 治疗前 45 分钟给予单次 7-NI 共同治疗。与没有 7-NI 治疗相比，运动障碍性 MPTP 处理的猴子的 LIDs 明显减少（<0.05）。在有和没有 7-NI 共同治疗的所有三只猴子中，L-DOPA 的抗帕金森作用相似。与 LIDs 的强度和持续时间相比，这种改善具有统计学意义，而 L-DOPA 治疗的有益作用得以维持，这可能代表一种改善 PD 患者生活质量的有前途的治疗方法。
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