Elsworth J D, Glover V, Reynolds G P, Sandler M, Lees A J, Phuapradit P, Shaw K M, Stern G M, Kumar P
Psychopharmacology (Berl). 1978 Apr 14;57(1):33-8. doi: 10.1007/BF00426954.
After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.
在用选择性单胺氧化酶B抑制剂(-)-司来吉兰进行预处理后,给予足以完全抑制血小板酶的剂量,4名正常志愿者和6名帕金森病志愿者(2名接受左旋多巴,2名接受左旋多巴加卡比多巴)在口服酪胺激发试验后,即使给予远高于正常饮食中可能遇到的剂量,也未出现不良升压反应(“奶酪效应”)。左旋多巴-司来吉兰组合本身也未引起升压反应。研究表明,正常人体肠道黏膜主要含有对司来吉兰不敏感的A型酶,该酶可能在接受司来吉兰治疗的志愿者体内降解摄入的酪胺;即使是长期接受该药物治疗的志愿者也未出现“奶酪效应”,这表明A型酶未受抑制。肠道单胺氧化酶A能够氧化多巴胺,而在人体血小板或纹状体中,多巴胺是单胺氧化酶B的底物。与酪胺一样,口服苯乙胺激发试验给予远高于正常饮食中已知含量的剂量,同样在接受(-)-司来吉兰治疗的受试者中未引起不良反应;其原因尚待确定。