Opezzo Javier A W, Höcht Christian, Taira Carlos A
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junĭn 956, 1113 Buenos Aires, Argentina.
Pharmacol Res. 2003 Jul;48(1):61-7.
Pharmacokinetics of methyldopa (MD) and the effect on the dopaminergic metabolism was studied in anesthetized sham-operated (SO) and sinoaortic-denervated (SAD) rats by using the microdialysis technique. A concentric microdialysis probe was placed in the striatum or in the posterior hypothalamus. Levels of MD, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC). Following the i.p. administration of MD (50 mg x kg(-1), i.p.), striatal dialysates showed that this drug rapidly reaches the brain. However, in SAD rats the MD levels of dialysates were lower and decreased more rapidly compared to SO rats. On the other hand, dialysates of posterior hypothalamus showed that in SAD animals the accumulation of MD was significantly greater than in SO rats.MD does not significantly reduce the striatal production of dopaminergic metabolite DOPAC in both groups of rats. The drug also induces a decrease of DOPAC levels in hypothalamic dialysates of SO and SAD animals. On the other hand, a no significative decay of HVA levels was seen in the striatal dialysate of both groups of experimental animals. In conclusion, this study by using a microdialysis technique shows that MD has different kinetic profiles in dialysates from posterior hypothalamus and striatum of SO and SAD rats at a dose that alters dopaminergic metabolism.
采用微透析技术，在麻醉的假手术（SO）大鼠和去窦弓神经（SAD）大鼠中研究了甲基多巴（MD）的药代动力学及其对多巴胺能代谢的影响。将同心微透析探针置于纹状体或下丘脑后部。通过高压液相色谱-电化学检测（HPLC-EC）测定MD、高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）的水平。腹腔注射MD（50mg·kg⁻¹，腹腔注射）后，纹状体透析液显示该药物迅速进入脑内。然而，与SO大鼠相比，SAD大鼠透析液中的MD水平较低且下降更快。另一方面，下丘脑后部的透析液显示，SAD动物中MD的蓄积明显大于SO大鼠。在两组大鼠中，MD均未显著降低纹状体中多巴胺能代谢产物DOPAC的产生。该药物还导致SO和SAD动物下丘脑透析液中DOPAC水平降低。另一方面，两组实验动物纹状体透析液中HVA水平均未见明显下降。总之，本研究采用微透析技术表明，在改变多巴胺能代谢的剂量下，MD在SO和SAD大鼠下丘脑后部和纹状体的透析液中具有不同的动力学特征。
