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R-司来吉兰:其活性的药理学谱

R-deprenyl: pharmacological spectrum of its activity.

作者信息

Magyar K, Szende B, Jenei V, Tábi T, Pálfi M, Szöko E

机构信息

Department of Pharmacodynamics, Semmelweis University, H-1445, Budapest, POB 370, Hungary.

出版信息

Neurochem Res. 2010 Dec;35(12):1922-32. doi: 10.1007/s11064-010-0238-8. Epub 2010 Aug 20.

Abstract

Deprenyl has been discovered by Knoll and co-workers. The R-enantiomer of deprenyl (selegiline) is a selective and irreversible inhibitor of the B-isoform of monoamine oxidase (MAO-B) enzyme. Due to its dopamine potentiating and possible neuroprotective properties it has an established role in the treatment of parkinsonian patients. By inhibiting MAO-B enzyme, R-deprenyl decreases the formation of hydrogen peroxide, alleviating the oxidative stress also reduced by increased expression of antioxidant enzymes (superoxide dismutases and catalase) reported during chronic treatment. It was shown to prevent the detrimental effects of neurotoxins like MPTP and DSP-4. R-Deprenyl elicits neuroprotective and neuronal rescue activities in concentrations too low to inhibit MAO-B. It is extensively metabolized and some of the metabolites possess pharmacological activities, thus their contribution to neuroprotective properties was also suggested. The recently identified deprenyl-N-oxide is extensively studied in our laboratory. Effects other than neuroprotection, like influencing cell adhesion and proliferation cannot be neglected.

摘要

司来吉兰是由诺尔及其同事发现的。司来吉兰的R-对映体(司来吉兰)是单胺氧化酶(MAO-B)B同工型的选择性不可逆抑制剂。由于其具有增强多巴胺的作用以及可能的神经保护特性,它在帕金森病患者的治疗中具有既定作用。通过抑制MAO-B酶,R-司来吉兰减少了过氧化氢的形成,减轻了氧化应激,慢性治疗期间报告的抗氧化酶(超氧化物歧化酶和过氧化氢酶)表达增加也降低了氧化应激。它被证明可以预防MPTP和DSP-4等神经毒素的有害影响。R-司来吉兰在浓度过低而无法抑制MAO-B时会引发神经保护和神经元拯救活性。它被广泛代谢,一些代谢产物具有药理活性,因此也有人提出它们对神经保护特性有贡献。我们实验室最近对新鉴定出的司来吉兰-N-氧化物进行了广泛研究。除神经保护作用外,影响细胞黏附和增殖等其他作用也不可忽视。

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