Pappu A S, Hauser G
J Neurochem. 1981 Oct;37(4):1006-14. doi: 10.1111/j.1471-4159.1981.tb04488.x.
Cationic amphiphilic drugs (CADs) of varied clinical use were screened to determine their capacity to alter the pattern of labeling with 32Pi of cerebral cortex mince phospholipids. The altered phospholipid labeling patterns were qualitatively similar, the prominent features being reduced incorporation into phosphatidylcholine and increased incorporation into phosphatidic acid. Relative potencies were: (/-+)-propranolol greater than chlorpromazine = 4,4'-bis(diethylaminoethoxy) alpha,beta-diethyldiphenylethane greater than desipramine greater than dibucaine greater than pimozide greater than oxymetazoline = fenfluramine = haloperidol = chloroquine greater than amphetamine = no drug added. Propranolol was used to study the action of CADs further. Its effect was time- and dose-dependent but in contrast with pineal gland, no label appeared in phosphatidyl-CMP (CDP-diacylglycerol), nor did dialysis of the mince to reduce diffusible substrates or exogenous addition of substrates cause appearance of liponucleotide. Thus lack of diffusible precursors is not responsible for CAD effects in vitro. Pulse-chase experiments with 32Pi and [2-3H]glycol suggested that inhibition of phosphatidate phosphohydrolase may be partly responsible for the observed alterations in phospholipid labeling in the presence of CADs.
对各种临床用途的阳离子两亲性药物（CADs）进行了筛选，以确定它们改变大脑皮层切碎组织磷脂用32Pi标记模式的能力。改变后的磷脂标记模式在质量上相似，突出特征是磷脂酰胆碱的掺入减少，磷脂酸的掺入增加。相对效力为：（±）-普萘洛尔大于氯丙嗪 = 4,4'-双（二乙氨基乙氧基）α,β-二乙基二苯乙烷大于地昔帕明大于丁卡因大于匹莫齐特大于羟甲唑啉 = 芬氟拉明 = 氟哌啶醇 = 氯喹大于苯丙胺 = 未添加药物。使用普萘洛尔进一步研究CADs的作用。其作用具有时间和剂量依赖性，但与松果体不同，磷脂酰-CMP（CDP-二酰甘油）中未出现标记，切碎组织的透析以减少可扩散底物或底物的外源添加也未导致脂核苷酸的出现。因此，缺乏可扩散前体不是CADs体外作用的原因。用32Pi和[2-3H]二醇进行的脉冲追踪实验表明，在存在CADs的情况下，观察到的磷脂标记改变可能部分归因于磷脂酸磷酸水解酶的抑制。
