Alpha-methyladrenaline: a possible active metabolite of alpha-methyldopa in the rat brain.

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.