Tung C S, Goldberg M R, Hollister A S, Oates J A, Robertson D
J Pharmacol Exp Ther. 1983 Nov;227(2):484-90.
We compared peripheral and central cardiovascular effects of (+/-)-alpha-methylepinephrine (alpha-ME) and (+/-)-alpha-methylnorepinephrine (alpha-MNE), two putative active metabolites of alpha-methyldopa to those of (-)-epinephrine in urethane-anesthetized normotensive rats. Intravenous administration of 1 microgram doses of alpha-ME (4.3 nmol) lowered blood pressure whereas alpha-MNE (4.5 nmol) and (-)-epinephrine (3.0 nmol) raised blood pressure. Heart rate responses to each were opposite to the blood pressure response, consistent with reflex buffering. When administered into the cerebral ventricle (5-20 micrograms) (15-90 nmol) and nucleus of the solitary tract (0.3-10 nmol), each catecholamine caused marked reductions in both blood pressure and heart rate. alpha-ME was more potent than alpha-MNE and the endogenous catecholamine, (-)-epinephrine, in its central depressor effect. The greater potency of alpha-ME relative to alpha-MNE and (-)-epinephrine suggests that it could contribute to antihypertensive actions of alpha-methyldopa.
我们在氨基甲酸乙酯麻醉的正常血压大鼠中，比较了（±）-α-甲基肾上腺素（α-ME）和（±）-α-甲基去甲肾上腺素（α-MNE）这两种α-甲基多巴的假定活性代谢产物与（-）-肾上腺素对周围和中枢心血管系统的影响。静脉注射1微克剂量的α-ME（4.3纳摩尔）可降低血压，而α-MNE（4.5纳摩尔）和（-）-肾上腺素（3.0纳摩尔）则可升高血压。对每种药物的心率反应与血压反应相反，这与反射缓冲作用一致。当将每种儿茶酚胺注入脑室（5-20微克）（15-90纳摩尔）和孤束核（0.3-10纳摩尔）时，均会导致血压和心率显著降低。α-ME在其对中枢的降压作用方面比α-MNE和内源性儿茶酚胺（-）-肾上腺素更强效。α-ME相对于α-MNE和（-）-肾上腺素的更强效性表明，它可能有助于α-甲基多巴的降压作用。
