Boomsma F, van den Meiracker A, Man in 't Veld A, Schalekamp M
Cardiovascular Research Institute COEUR, University Hospital Dijkzigt/Erasmus University, Rotterdam, The Netherlands.
Life Sci. 1995;57(19):1753-9. doi: 10.1016/0024-3205(95)02153-a.
The peripheral decarboxylase inhibitors benserazide and carbidopa, often administered in combination with L-dopa in the treatment of Parkinson's disease, are also very good inhibitors of semicarbazide-sensitive amine oxidase (SSAO). In untreated patients and in patients treated with L-dopa alone, plasma SSAO activity is normal. In patients treated with L-dopa plus benserazide or carbidopa (Madopar or Sinemnet), however, plasma SSAO activity is strongly inhibited, contrary to the paradoxical 3-fold increase in plasma aromatic-L-amino acid decarboxylase activity we reported previously. Single-dose and longitudinal studies show that the SSAO inhibition proceeds rapidly and increases even further to nearly complete inhibition after continued treatment, while aromatic-L-amino acid decarboxylase activity only transiently decreases after a single dose and increases slowly with continued treatment above pretreatment levels. Dialysis experiments confirm that the binding of benserazide to SSAO is irreversible, especially after chronic treatment. The lack of knowledge about the exact function of SSAO precludes definite conclusions about the effect of this chronic SSAO inhibition on patients. Careful follow-up studies of patients treated with Madopar or Sinemet might provide further information about the possible physiological role of SSAO.
外周脱羧酶抑制剂苄丝肼和卡比多巴在治疗帕金森病时常常与左旋多巴联合使用，它们也是氨基脲敏感胺氧化酶（SSAO）的良好抑制剂。在未经治疗的患者以及仅接受左旋多巴治疗的患者中，血浆SSAO活性正常。然而，在接受左旋多巴加苄丝肼或卡比多巴（美多芭或息宁）治疗的患者中，血浆SSAO活性受到强烈抑制，这与我们之前报道的血浆芳香族L-氨基酸脱羧酶活性出现矛盾的3倍增加相反。单剂量和纵向研究表明，SSAO抑制作用迅速发生，持续治疗后甚至会进一步增强至几乎完全抑制，而芳香族L-氨基酸脱羧酶活性仅在单剂量后短暂降低，并随着持续治疗缓慢升高至高于治疗前水平。透析实验证实，苄丝肼与SSAO的结合是不可逆的，尤其是在长期治疗后。由于对SSAO的确切功能缺乏了解，无法就这种长期SSAO抑制对患者的影响得出明确结论。对接受美多芭或息宁治疗的患者进行仔细的随访研究可能会提供有关SSAO可能的生理作用的更多信息。
