Himeno A, Kunisada K, Niwa M, Ozaki M
Jpn J Pharmacol. 1985 Sep;39(1):91-8. doi: 10.1254/jjp.39.91.
To determine whether or not alpha-methyladrenaline (MA) is an active metabolite of alpha-methyldopa, a centrally-acting hypotensive compound, we measured MA in the rat brain using the high-performance liquid chromatographic electrochemical detection method. After five daily treatments of alpha-methyldopa given twice daily a dose of 40 mg/kg, we found trace amounts of MA in the hypothalamus and C1-C2 area (hypothalamus, 23.7 +/- 2.3 picomole/g, n = 7; C1-C2 area, 5.4 +/- 0.4 picomole/g, n = 4), as well as large amounts of alpha-methylnoradrenaline (MNA) (Hypothalamus, 16.6 +/- 0.4 nanomole/g, n = 7; C1-C2 area, 7.0 +/- 0.2 nanomole/g, n = 4). In these brain areas, the amount of endogenous adrenaline was reduced to 10.6% and 16.1% of the control values, respectively. The amounts of MA were only 9.0% and 6.2% of that of endogenous adrenaline in these respective areas whereas MNA was detected at approximately the same level as endogenous noradrenaline. These findings indicate that MA is synthesized from alpha-methyldopa to a very minute extent in the hypothalamus and C1-C2 area, and a large amount of MNA was synthesized in these areas. These are of interest considering the changes of endogenous adrenaline and noradrenaline. Our results raise doubts about the participation of MA on the main determinant of the central hypotensive effect of alpha-methyldopa.
为了确定α-甲基肾上腺素（MA）是否是中枢性降压化合物α-甲基多巴的活性代谢产物，我们采用高效液相色谱电化学检测法测定了大鼠脑中的MA。在每天两次给予40mg/kg剂量的α-甲基多巴，连续处理五天后，我们在下丘脑和C1 - C2区域（下丘脑，23.7±2.3皮摩尔/克，n = 7；C1 - C2区域，5.4±0.4皮摩尔/克，n = 4）发现了痕量的MA，以及大量的α-甲基去甲肾上腺素（MNA）（下丘脑，16.6±0.4纳摩尔/克，n = 7；C1 - C2区域，7.0±0.2纳摩尔/克，n = 4）。在这些脑区，内源性肾上腺素的量分别降至对照值的10.6%和16.1%。在这些相应区域中，MA的量仅为内源性肾上腺素量的9.0%和6.2%，而检测到的MNA水平与内源性去甲肾上腺素大致相同。这些发现表明，MA在下丘脑和C1 - C2区域由α-甲基多巴合成的程度非常微小，并且在这些区域合成了大量的MNA。考虑到内源性肾上腺素和去甲肾上腺素的变化，这些结果是有趣的。我们的结果对MA参与α-甲基多巴中枢降压作用的主要决定因素提出了质疑。
