Treseder S A, Rose S, Summo L, Jenner P
Neurodegenerative Disease Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College, London, United Kingdom.
J Neural Transm (Vienna). 2003 Mar;110(3):229-38. doi: 10.1007/s00702-002-0778-4.
The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat. In vitro, carbidopa, benserazide and NSD-1015 all potently inhibited hepatic MAO A and B activity (IC(50) 10-50 micro M). In ex vivo studies following systemic drug administration, NSD-1015 (100 mg/kg ip) produced 88% and 96% inhibition of hepatic and striatal MAO A and B activity respectively. Carbidopa (12.5 mg/kg i.p.) and benserazide (50 mg/kg i.p.) had no effect on striatal MAO A activity or hepatic MAO B activity. However, they inhibited striatal MAO B activity by 45 +/- 10% and 36 +/- 10% respectively. In conclusion, carbidopa and benserazide may not only protect L-DOPA from peripheral decarboxylation, but also increase striatal dopamine content through MAO inhibition. NSD-1015 should not be used to investigate the neuromodulatory role of L-DOPA as it potently inhibits rat striatal MAO.
研究了外周芳香族氨基酸脱羧酶（AADC）抑制剂卡比多巴和苄丝肼以及中枢AADC抑制剂3-羟基苄肼（NSD-1015）对大鼠外周和脑单胺氧化酶（MAO）A和B活性的影响。在体外，卡比多巴、苄丝肼和NSD-1015均能有效抑制肝脏MAO A和B的活性（半数抑制浓度[IC(50)]为10 - 50微摩尔）。在全身给药后的离体研究中，NSD-1015（腹腔注射100毫克/千克）分别对肝脏和纹状体MAO A和B的活性产生了88%和96%的抑制作用。卡比多巴（腹腔注射12.5毫克/千克）和苄丝肼（腹腔注射50毫克/千克）对纹状体MAO A活性或肝脏MAO B活性没有影响。然而，它们分别使纹状体MAO B活性抑制了45±10%和36±10%。总之，卡比多巴和苄丝肼不仅可以保护左旋多巴不被外周脱羧，还可通过抑制MAO增加纹状体多巴胺含量。由于NSD-1015能有效抑制大鼠纹状体MAO，因此不应使用它来研究左旋多巴的神经调节作用。
