Da Prada M, Keller H H, Kettler R
Pharmazeutische Forschungsabteilung, F. Hoffmann-La Roche & Co. AG, Basel.
Psychiatr Prax. 1989 Aug;16 Suppl 1:18-24.
The rat studies presented in this manuscript show that the new non-hydrazine compounds moclobemide, brofaromine and toloxatone have a profile typical of monoamine oxidase-A (MAO-A) inhibitors. These inhibitors are short-acting (16-24 h), reversible, non-hepatotoxic and have only low liability to potentiate tyramine pressor effects (cheese-effect). The present results in rats and the clinical trials provide evidence that moclobemide is an orally active MAO-A inhibitor which, due to its remarkably low tyramine potentiating pressor effects and to its lack of anticholinergic activity, has a very attractive pharmacological profile. In contrast to moclobemide, tranylcypromine is an irreversible and mixed MAO-A and MAO-B inhibitor with long-lasting effects. This hydrazine derivative is not devoid of hepatotoxic effects and markedly potentiates tyramine pressor effects. Moclobemide, being a particularly safe MAO-A inhibitor, seems to be an effective new compound for the therapy of exogenous and endogenous depressive states.
本手稿中呈现的大鼠研究表明,新型非肼类化合物吗氯贝胺、溴法罗明和托洛沙酮具有单胺氧化酶-A(MAO-A)抑制剂的典型特征。这些抑制剂作用时间短(16 - 24小时)、可逆、无肝毒性,且增强酪胺升压效应(奶酪效应)的可能性很低。目前在大鼠身上的研究结果以及临床试验表明,吗氯贝胺是一种口服活性MAO-A抑制剂,由于其显著低的酪胺升压效应增强作用以及缺乏抗胆碱能活性,具有非常吸引人的药理学特性。与吗氯贝胺相反,反苯环丙胺是一种不可逆的MAO-A和MAO-B混合抑制剂,作用持久。这种肼衍生物并非没有肝毒性作用,且能显著增强酪胺升压效应。吗氯贝胺作为一种特别安全的MAO-A抑制剂,似乎是治疗外源性和内源性抑郁状态的一种有效新化合物。