Sandler M, Glover V, Ashford A, Stern G M
J Neural Transm. 1978;43(3-4):209-15. doi: 10.1007/BF01246957.
Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.
尽管选择性单胺氧化酶(MAO)B抑制剂(-)司来吉兰在人体经酪胺激发试验后已证明不存在“奶酪效应”,但其原因尚不清楚:这很可能与该药物的选择性抑制作用无关,因为在长期给药过程中,有证据表明该酶的A和B两种形式均受到同等程度的抑制。在预先用司来吉兰处理的猪(之所以选择猪,是因为它在所有其他组织中仅含有MAO B)中,通过静脉注射酪胺绕过假定的MAO A肠道屏障,尽管MAO受到了显著抑制,但并未引发升压反应。相反,氯吉兰(MAO A抑制剂)预处理虽然导致MAO抑制作用最小,却产生了强烈的高血压反应,类似于使用非MAO抑制药物异烟肼时观察到的反应。对这些发现最简洁的解释可能是,“传统”MAO抑制剂通常会产生两种独立但密切相关的药理作用,即适当的酶抑制作用以及在酪胺激发试验期间促进去甲肾上腺素从其结合位点释放。