Engelman K, Horwitz D, Jéquier E, Sjoerdsma A
J Clin Invest. 1968 Mar;47(3):577-94. doi: 10.1172/JCI105754.
Alpha methyltyrosine (alpha-MPT) was administered to 52 patients from 4 days to 10 months; 22 patients were cases of pheochromocytoma and 20 had essential hypertension. Inhibition of catecholamine synthesis in the range of 50-80% was achieved with divided daily drug dosage of from 1.0 to 4.0 g. Striking clinical benefit was noted in patients with pheochromocytoma in whom the drug was used in preparation for surgery and during chronic medical management. The drug appeared to have limited usefulness when used in essential hypertension, unless added to existing therapy with conventional agents. No beneficial effects were noted in thyrotoxicosis, glaucoma, and Raynaud's phenomenon. Untoward effects in order of decreasing incidence were: sedation (with insomnia on withdrawal), anxiety, tremor, diarrhea, and galactorrhea. Drug crystalluria, which has been observed in animals and is currently restrictive of clinical trials, was not observed in these studies. Evidence is presented that the minor conversion of alpha-MPT to methyldopa probably does not contribute significantly to the central and peripheral effects of the drug.
对52例患者给予α-甲基酪氨酸(α-MPT),用药时间为4天至10个月;其中22例为嗜铬细胞瘤患者,20例为原发性高血压患者。通过每日1.0至4.0 g的分次给药剂量,儿茶酚胺合成的抑制率达到了50%-80%。在用于嗜铬细胞瘤患者手术准备和慢性药物治疗期间,该药显示出显著的临床益处。在原发性高血压患者中使用时,该药似乎作用有限,除非与现有常规药物联合使用。在甲状腺毒症、青光眼和雷诺现象中未观察到有益效果。不良反应发生率由高到低依次为:镇静(停药后出现失眠)、焦虑、震颤、腹泻和溢乳。在动物中观察到的药物结晶尿目前限制了临床试验,但在这些研究中未观察到。有证据表明,α-MPT向甲基多巴的少量转化可能对该药的中枢和外周作用没有显著贡献。