Actions of chlorpromazine, haloperidol and pimozide on lipid metabolism in guinea pig brain slices.
Actions of chlorpromazine, haloperidol and pimozide on lipid metabolism in guinea pig brain slices.
复制标题
氯丙嗪、氟哌啶醇和匹莫齐特对豚鼠脑片脂质代谢的作用。
DOI：
10.1016/0006-2952(80)90092-1
复制
发表时间：
1980
影响因子：
5.8
通讯作者：
Hokin-Neaverson,M
中科院分区：
文献类型：
--
作者：
Hokin-Neaverson,M
氯丙嗪导致磷脂酸和磷脂酰肌醇在豚鼠和大鼠脑切片中代谢的增加，如通过掺入各种放射性前体所测量的[I，21。磷脂酰胆碱和磷脂酰乙醇胺的代谢没有增加。其他几种阳离子两亲性药物在各种组织中具有类似的作用[3]。该效应似乎涉及通过CDP-二酰甘油途径合成的磷脂酸和磷脂（如磷脂酰肌醇）的新生合成增加。在这方面，它不同于某些神经递质对磷脂酰肌醇代谢的受体介导作用，后者增加了脂质中磷酸盐和肌醇的周转，而没有伴随二酰基甘油部分的合成[4]。有人认为，氯丙嗪和其他药物对磷脂代谢的影响可能与药物的临床作用机制有关[2，3]。在目前的工作中，氯丙嗪，氟哌啶醇和匹莫齐特的行动进行了比较，以确定这些药物对磷脂代谢的影响是否可能与其抗精神病活性。这三种化合物是临床上用作精神安定剂的吩噻嗪、丁酰苯和二苯基丁基哌啶类药物的代表。还检查了它们与去甲肾上腺素和多巴胺对磷脂代谢的影响的相互作用。
Chlorpromazine causes an increase in the metabolism of phosphatidic acid and phosphatidylinositol in guinea pig and rat brain slices, as measured by the incorporation of various radioactive precursors [I, 21. The metabolism of phosphatidylcholine and phosphatidylethanolamine is not increased. Several other cationic amphophilic drugs have similar effects in various tissues [3]. The effect appears to involve increased synthesis de nova of phosphatidic acid and of phospholipids such as phosphatidylinositol that are synthesized via the CDP-diacylglycerol pathway. In this respect it differs from the receptor-mediated effect of some neurotransmitters on the metabolism of phosphatidylinositol, in which there is an increased turnover of phosphate and inositol in the lipid, without a concomitant synthesis of the diacylglycerol moiety [4]. It has been suggested that the effects of chlorpromazine and other drugs on phospholipid metabolism may be related to the clinical mechanisms of action of the drugs [2, 3]. In the present work, the actions of chlorpromazine, haloperidol and pimozide were compared to determine whether effects of these drugs on phospholipid metabolism might be correlated with their neuroleptic activity. These three compounds are representative of the phenothiazine, butyrophenone and diphenylbutylpiperidine classes of drugs that are used clinically as neuroleptic agents. Their interactions with effects of norepinephrine and dopamine on phospholipid metabolism were also examined.