Wu W R, Zhu X Z, Guan H J, Wang R G, Ji X Q
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhongguo Yao Li Xue Bao. 1999 Feb;20(2):146-50.
To study the neuroprotective, neurorescue, neurorestorative effects of selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inhibition of brain monoamine oxidase B (MAO-B).
The striatal levels of dopamine and its metabolites were measured using HPLC with electrochemical detection (HPLC-EC). The inhibition of MAO-B was tested by an improved fluorimetric assay.
1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) (30 mg.kg-1 i.p.) reduced the striatal dopamine level by 73% in mice. Selegiline (Sel, 10 mg.kg-1 i.p.) before, but not after, MPTP treatment protected against MPTP-induced nigrostriatal dopaminergic neurotoxicity. There were no differential effects between Sel and saline treatments on the recovery of striatal dopamine levels, which were partially restored during 2 wk. 1-Methyl-4-phenylpyridinium (MPP+) (5 mg.kg-1 i.p.) produced no dopaminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inhibited mouse brain MAO-B in vitro (IC50 = 17 nmol.L-1, 95% confidence limits = 14-20 nmol.L-1).
Selegiline has neuroprotective rather than neurorescue or neurorestorative effects on MPTP-induced nigrostriatal dopaminergic neuronal degeneration, which is directly pertinent to its selective and irreversible inhibition of brain MAO-B activity.
研究司来吉兰（Sel）对黑质纹状体多巴胺能神经元系统的神经保护、神经挽救及神经修复作用，以及其对脑单胺氧化酶B（MAO - B）的抑制作用。
采用高效液相色谱 - 电化学检测法（HPLC - EC）测定纹状体中多巴胺及其代谢产物的水平。通过改进的荧光测定法检测MAO - B的抑制情况。
1 - 甲基 - 4 - 苯基 - 1,2,3,6 - 四氢吡啶（MPTP）（30 mg·kg-1腹腔注射）使小鼠纹状体多巴胺水平降低73%。在MPTP治疗前而非治疗后给予司来吉兰（Sel，10 mg·kg-1腹腔注射）可预防MPTP诱导的黑质纹状体多巴胺能神经毒性。Sel与生理盐水治疗对纹状体多巴胺水平恢复的影响无差异，在2周内纹状体多巴胺水平部分恢复。1 - 甲基 - 4 - 苯基吡啶离子（MPP+）（5 mg·kg-1腹腔注射）未产生多巴胺能神经毒性。此外，Sel在体外可选择性且不可逆地抑制小鼠脑MAO - B（IC50 = 17 nmol·L-1，95%置信区间 = 14 - 20 nmol·L-1）。
司来吉兰对MPTP诱导的黑质纹状体多巴胺能神经元变性具有神经保护作用而非神经挽救或神经修复作用，这与其对脑MAO - B活性的选择性及不可逆抑制直接相关。
