Zavisca F G, Breau A P, Wurtman R J
Circ Res. 1979 Nov;45(5):684-90. doi: 10.1161/01.res.45.5.684.
We studied the effect of 3-O-methyl-methyldopa (OMMD), the 3-O-methylated metabolite of the antihypertensive drug methyldopa (alpha-methyldopa, AMD), on blood pressure in the spontaneously hypertensive rat. OMMD lowered blood pressure in a dose-related manner when given orally or intraperitoneally. Its action lasted longer than that of AMD, and daily oral administration produced a cumulative fall in blood pressure. Oral and intraperitoneal OMMD produced similar reductions of blood pressure and similar tissue OMMD levels. After intraperitoneal injection of different doses, levels of OMMD measured in brain, spinal cord, and plasma correlated with the magnitude of the antihypertensive effect. No AMD was detected in tissues after either route of administration, which suggests that the antihypertensive effect was not based on demethylation of OMMD to AMD. Peripheral inhibition of the enzyme, aromatic amino acid decarboxylase (AAAD), failed to suppress OMMD's effect on blood pressure; in contrast, central inhibition of AAAD did decrease OMMD's antihypertensive effect. These observations suggest that 3-O-methylated metabolites may participate in the antihypertensive effect of AMD.
我们研究了抗高血压药物甲基多巴（α-甲基多巴，AMD）的3-O-甲基化代谢产物3-O-甲基-甲基多巴（OMMD）对自发性高血压大鼠血压的影响。口服或腹腔注射OMMD时，其可使血压呈剂量依赖性降低。其作用持续时间比AMD更长，每日口服可使血压累积下降。口服和腹腔注射OMMD产生的血压降低幅度相似，组织中OMMD水平也相似。腹腔注射不同剂量后，在脑、脊髓和血浆中测得的OMMD水平与降压效果的大小相关。两种给药途径后组织中均未检测到AMD，这表明降压作用并非基于OMMD脱甲基化为AMD。外周抑制芳香族氨基酸脱羧酶（AAAD）未能抑制OMMD对血压的作用；相反，中枢抑制AAAD确实降低了OMMD的降压作用。这些观察结果表明，3-O-甲基化代谢产物可能参与了AMD的降压作用。
