Ferris R M, Cooper B R, Maxwell R A
J Clin Psychiatry. 1983 May;44(5 Pt 2):74-8.
The data obtained in these studies show that the antidepressant activity of bupropion cannot be explained by its ability to inhibit MAO present in brain or to increase the release of biogenic amines from nerve endings, since the drug possesses neither of these properties. It is also unlikely that the weak properties of the drug as an inhibitor of dopamine uptake in brain can explain its antidepressant activity. It is clear, however, that dopamine neurons must be present for the CNS properties of bupropion to be manifested in animal models; at antidepressant doses of the drug, dopamine turnover is reduced in brain. Finally, the antidepressant properties of bupropion have been dissociated from down-regulation of postsynaptic beta-receptors. To our knowledge, bupropion is the first clinically effective antidepressant whose mechanism of action cannot be explained on the basis of alterations in either presynaptic events or postsynaptic receptor-mediated events in catecholamine or serotonin pathways. Thus, bupropion is a novel antidepressant whose mechanism of action must still be elucidated.
这些研究中获得的数据表明，安非他酮的抗抑郁活性无法通过其抑制脑中单胺氧化酶（MAO）的能力或增加神经末梢生物胺释放的能力来解释，因为该药物不具备这两种特性。该药物作为脑中多巴胺摄取抑制剂的微弱特性也不太可能解释其抗抑郁活性。然而，很明显，安非他酮的中枢神经系统特性要在动物模型中表现出来，多巴胺神经元必须存在；在该药物的抗抑郁剂量下，脑中多巴胺的更新率会降低。最后，安非他酮的抗抑郁特性与突触后β受体的下调无关。据我们所知，安非他酮是第一种临床有效的抗抑郁药，其作用机制无法基于儿茶酚胺或5-羟色胺途径中突触前事件或突触后受体介导事件的改变来解释。因此，安非他酮是一种新型抗抑郁药，其作用机制仍有待阐明。
