Lavian G, Finberg J P, Youdim M B
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Clin Neuropharmacol. 1993;16 Suppl 2:S1-7.
Severe side effects such as hepatotoxicity and potentiation of the sympathomimetic action of tyramine ("the cheese effect") caused the withdrawal of nonselective irreversible monoamine oxidase (MAO) inhibitors from use in psychiatric therapy. The development of selective irreversible inhibitors for MAO type A did not eliminate cardiovascular side effects such as "the cheese effect" or, conversely, the hypotensive effect of these drugs. To overcome at least "the cheese effect," selective reversible MAO-A inhibitor antidepressants such as moclobemide and brofaromine have been developed. Being reversibly bound to MAO, these drugs may be displaced from their binding site in the intestine by ingested, indirectly sympathomimetic amines such as tyramine, thus avoiding the initiation of the hypertensive crises. Using a rat renal nerve preparation, we have demonstrated that acute administration of either moclobemide or brofaromine (10 mg/kg) does not cause a decrease in blood pressure or a significant reduction in sympathetic renal nerve activity. These data contrast with those obtained with clorgyline or desipramine. The results indicate that moclobemide and brofaromine may be devoid of a hypotensive effect, including orthostatic hypotension.
严重的副作用，如肝毒性以及酪胺拟交感神经作用的增强（“奶酪效应”），导致非选择性不可逆单胺氧化酶（MAO）抑制剂退出精神科治疗领域。A型单胺氧化酶选择性不可逆抑制剂的研发并未消除诸如“奶酪效应”之类的心血管副作用，反之，也未能消除这些药物的降压作用。为了至少克服“奶酪效应”，人们研发了选择性可逆MAO-A抑制剂抗抑郁药，如吗氯贝胺和溴法罗明。由于这些药物与单胺氧化酶是可逆性结合，摄入的间接拟交感神经胺（如酪胺）可将它们从肠道的结合位点上置换下来，从而避免引发高血压危象。我们利用大鼠肾神经制备物证明，急性给予吗氯贝胺或溴法罗明（10毫克/千克）不会导致血压下降或肾交感神经活动显著降低。这些数据与用氯吉兰或地昔帕明所获得的数据形成对比。结果表明，吗氯贝胺和溴法罗明可能没有降压作用，包括体位性低血压。
