Goldberg M R, Gerkens J F, Oates J A, Robertson D
Eur J Pharmacol. 1981 Jan 5;69(1):95-9. doi: 10.1016/0014-2999(81)90606-3.
The presence of phenylethanolamine-N-methyl transferase in those brain-stem nuclei where methyldopa is thought to act suggested to us that methylepinephrine could be an active metabolite of methyldopa. We assessed the potential of methylepinephrine to be an active metabolite by determining its capacity to compete for ligands which bind to alpha-receptors in rat brain. Thus, the abilities of epinephrine, norepinephrine, methyldopa, (+/-)-methylnorepinephrine and (+/-)-methylepinephrine to compete for alpha 1-([3H]WB-4101) and alpha 2-([3H]clonidine) binding sites in rat brain wee compared. Order of potency at each binding site was: [3H]WB-4101 -- (-)epinephrine = (-)-norepinephrine greater than (+/-)-methylnorepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa; [3H]clonidine -- (-)-epinephrine greater than (+/-)-methylnorepinephrine greater than (-)-norepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa. Since it can compete with a specific ligand for alpha 2-receptors, methylepinephrine could be a centrally active metabolite of methyldopa.
在甲基多巴被认为起作用的那些脑干核中存在苯乙醇胺 - N - 甲基转移酶，这使我们想到甲基去甲肾上腺素可能是甲基多巴的一种活性代谢产物。我们通过测定甲基去甲肾上腺素竞争与大鼠脑内α受体结合的配体的能力，来评估其作为活性代谢产物的潜力。因此，比较了肾上腺素、去甲肾上腺素、甲基多巴、（±）-甲基去甲肾上腺素和（±）-甲基去甲肾上腺素竞争大鼠脑内α1 - （[3H]WB - 4101）和α2 - （[3H]可乐定）结合位点的能力。在每个结合位点的效力顺序为：[3H]WB - 4101——（-）肾上腺素 = （-）-去甲肾上腺素 ＞ （±）-甲基去甲肾上腺素 ＞ （±）-甲基去甲肾上腺素 ＞＞ （-）-甲基多巴；[3H]可乐定——（-）-肾上腺素 ＞ （±）-甲基去甲肾上腺素 ＞ （-）-去甲肾上腺素 ＞ （±）-甲基去甲肾上腺素 ＞＞ （-）-甲基多巴。由于甲基去甲肾上腺素能与特定配体竞争α2受体，所以它可能是甲基多巴的一种中枢活性代谢产物。
