Katz R J, Lott M, Landau P, Waldmeier P
Development Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Biol Psychiatry. 1993 Feb 15;33(4):261-6. doi: 10.1016/0006-3223(93)90292-l.
The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized parallel clinical trials conducted serially, we examined the significance of NA uptake for antidepressant activity. The racemic compound oxaprotiline (hydroxymaprotiline) is a highly specific inhibitor of NA uptake, whereas its R-(-) enantiomer levoprotiline is totally devoid of this property. Oxaprotiline significantly resembled amitriptyline in its antidepressant potential. Conversely, levoprotiline significantly resembled placebo in antidepressant potential. Therefore, NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant.
抑郁症的去甲肾上腺素（NA）假说主要基于临床前和临床间接证据。在两项连续进行的三部分随机平行临床试验中，我们研究了NA摄取对抗抑郁活性的重要性。消旋化合物奥沙普替林（羟甲丙替林）是一种高度特异性的NA摄取抑制剂，而其R-(-)对映体左普替林则完全没有这种特性。奥沙普替林在抗抑郁潜力方面与阿米替林显著相似。相反，左普替林在抗抑郁潜力方面与安慰剂显著相似。因此，NA摄取对于这种实验性抗抑郁药所观察到的治疗效果是必要的。
