阿波啡对映体和多巴胺的自由基清除特性:可能与它们在帕金森病中的作用机制有关。

E E Sam, N Verbeke
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引用次数: 42

摘要

研究了R(-)阿波啡、S(+)阿波啡和多巴胺对两种多不饱和脂肪酸(胆固醇亚油酸酯(CL)和三叶油苷(TL))氧化动力学的影响。在50℃恒温的磷酸盐缓冲液(pH 7.4)中,2.2′-偶氮(2-甲基丙腈)(AMPN)在热分解过程中产生的自由基引发氧化,形成的氢过氧化物在290nm处用二极管阵列分光光度计碘滴定测定。阿波啡对映体和多巴胺都有抑制作用。生育酚(α -生育酚)和抗坏血酸作为对照。前者抑制氧化反应,而抗坏血酸促进氧化反应。这些结果与氧化损伤在帕金森病中的可能作用以及阿帕吗啡在提高“开关”发作中的有用性有关。在此基础上,我们提出了阿波啡的非多巴胺能对映体(S(+)-异构体),以测试其清除自由基在帕金森病中的重要性,最终可能导致副作用更小的治疗替代方案。
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Free radical scavenging properties of apomorphine enantiomers and dopamine: possible implication in their mechanism of action in parkinsonism.

The influence of R(-) apomorphine, S(+) apomorphine and dopamine on the oxidation kinetics of two polyunsaturated fatty acids (PUFA) (cholesteryl linoleate (CL) and Trilinolein (TL)) was investigated. The oxidation was initiated by free radicals generated through thermal decomposition of 2.2'-Azobis(2-methyl-propionitrile) (AMPN) in phosphate buffer (pH 7.4) thermostated at 50 degrees C. The hydroperoxides formed were determined by iodine titration using a diode array spectrophotometer at 290nm. Both enantiomers of apomorphine as well as dopamine exerted an inhibitory effect. Tocopherol (alpha-tocopherol) and ascorbic acid were used as controls. The former inhibited while ascorbic acid facilitated the oxidation reaction. These results are discussed in relation with the possible role of oxidative injury in parkinsonism and the usefulness of apomorphine in elevating "on-off" episodes. On this basis, the non-dopaminergic enantiomer of apomorphine (S(+)-isomer) is put foward to test the importance of its radical scavenging properties in parkinsonism which could eventually lead to a therapeutic alternative with less side effects.

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