Jonkers N, Sarre S, Ebinger G, Michotte Y
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, Belgium.
J Neural Transm (Vienna). 2001;108(5):559-70. doi: 10.1007/s007020170056.
In Parkinsonian patients treated with levodopa, peripheral decarboxylase inhibitors like carbidopa and benserazide are used to increase the central availability of levodopa. In experimental animal studies, this clinical situation is mimicked. However, at the dose used in many animal studies, both benserazide and carbidopa pass the blood brain barrier. In this study, we investigated to what extent their presence in brain inhibits striatal aromatic amino acid decarboxylase activity. At 50 mg/kg i.p., both carbidopa and benserazide decreased striatal decarboxylase activity. At 10 mg/kg i.p., only benserazide decreased the enzyme activity, but this did not change extracellular dopamine in striatum and allowed dopamine levels to increase after levodopa administration. In contrast, the inhibition of central decarboxylase activity by 50 mg/kg benserazide decreased striatal dopamine levels and prevented the levodopa-induced increase. Therefore, it is important to carefully consider the dose of the peripheral decarboxylase inhibitor used when the central effects of levodopa are studied.
在接受左旋多巴治疗的帕金森病患者中，外周脱羧酶抑制剂如卡比多巴和苄丝肼被用于提高左旋多巴在中枢的可用性。在实验动物研究中，模拟了这种临床情况。然而，在许多动物研究中使用的剂量下，苄丝肼和卡比多巴都能通过血脑屏障。在本研究中，我们调查了它们在脑内的存在对纹状体芳香族氨基酸脱羧酶活性的抑制程度。腹腔注射50mg/kg时，卡比多巴和苄丝肼均降低了纹状体脱羧酶活性。腹腔注射10mg/kg时，只有苄丝肼降低了酶活性，但这并未改变纹状体内的细胞外多巴胺水平，且在给予左旋多巴后多巴胺水平升高。相比之下，50mg/kg苄丝肼对中枢脱羧酶活性的抑制降低了纹状体多巴胺水平，并阻止了左旋多巴诱导的多巴胺水平升高。因此，在研究左旋多巴的中枢作用时，仔细考虑所用外周脱羧酶抑制剂的剂量非常重要。
