TYROSINE FOR THE TREATMENT OF DEPRESSION

儿茶酚胺（CA）假说将抑郁症解释为缺乏 去甲肾上腺素（NE）在特定的大脑位点，并与此一致， 几乎所有可用的抗抑郁药都增强脑NE活性。 然而 现有的抗抑郁药是不完善的，因为起效缓慢， 许多不必要的影响。 酪氨酸是NE的氨基酸前体， 已经显示出增强实验动物大脑中的NE活性， 人类的初步数据表明，它可能有潜力成为一种 抗抑郁药 此外，可能的是， 酪氨酸，或酪氨酸浓度与其他酪氨酸浓度的比率。 大的中性氨基酸与之竞争进入大脑， 可以识别最有可能对酪氨酸产生反应的抑郁症患者， 疗法 也可以认为，血药浓度增加或 酪氨酸治疗过程中的酪氨酸比值可能与临床 改进. 最后，可以假设， 尿排泄MHPG（NE的主要代谢产物），可能有低 脑NE周转水平，可能更有可能对酪氨酸 治疗学 为了验证这些临床和生化假设， 将酪氨酸与标准抗抑郁药物进行对比，我们建议 75例非双相抑郁症患者服用酪氨酸、丙咪嗪和安慰剂 在一个平行组，双盲协议。 失败的患者 改善安慰剂或丙咪嗪治疗可能随后治疗 用酪氨酸开放标记，提供部分交叉特征。 重要 治疗前和治疗期间要研究的生化变量包括 血浆氨基酸浓度和尿MHPG排泄。

The catecholamine (CA) hypothesis explains depression as a deficiency of norepinephrine (NE) at specific brain loci, and consistent with this, almost all available antidepressant drugs enhance brain NE activity. Yet available antidepressants are imperfect because of slow onset of actio and numerous unwanted effects. Tyrosine, the amino acid precursor of NE, has been shown to enhance NE activity in the brains of experimental animals, and preliminary data in humans suggest it may have potential as an antidepressant. Moreover, it is possible that plasma concentrations of tyrosine, or the ratio of the tyrosine concentration oto those of other large neutral amino acids with which it competes for uptake into the brain, may identify depressed patients who are most likely to respond to tyrosine therapy. It is also conceivalbethat increases in plasma concentration or the tyrosine ratio during tyrosine theraphy may correlate with clinical improvement. Finally, it could be hypothesized that individuals with low urinary excretio of MHPG (the major metabolite of NE), who may have a low level of brain NE turnover, might be more likely to respond to tyrosine theraphy. To test these clinical and biochemical hypotheses, and to contrast tyrosine to a standard antidepressant drug, we propose to administer tyrosine, imipramine, and placebo to 75 non-bipolar depressed oupatients in a parallel-group, double-blind protocol. Patients who fail to improve on placebo or imipramine therapy may subsequently be treated open-lable with tyrosine, providing a partial crossover feature. Important biochemical variables to be studied before and during treatment include plasma amino acid concentrations and urinary excretion of MHPG.