抗精神病药物与蔗糖酶的相互作用、动力学及结构研究。

IF 3.2 Q2 Pharmacology, Toxicology and Pharmaceutics
Narges Jafari, Helia Dehganpour, Nava Ghavanini, H. Mollasalehi, D. Minai-Tehrani
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引用次数: 2

摘要

背景在先天性蔗糖酶异麦芽糖酶缺乏症(CSID)患者中,应用酵母蔗糖酶悬浮液作为补偿酶缺乏的药物。虽然抗精神病药物用于治疗精神分裂症,但同时服用多种药物可能会相互抵消。方法研究三氟拉嗪和氟哌啶醇作为抗精神病药物对口服药物酵母蔗糖酶的相互作用。在这方面,酶的动力学参数是在药物存在或不存在的情况下测定的。还计算了药物的动力学参数,如Ki和IC50。Lineweaver-Burk图用于揭示抑制类型。结果两种药物均能通过非竞争性抑制降低蔗糖酶活性,降低酶的Vmax。氟哌啶醇和三氟哌嗪的药物的IC50和Ki值分别为0.7和0.068mM以及0.45和0.063mM。结果表明,三氟哌嗪与该酶的结合亲和力高于氟哌啶醇。荧光测量用于药物的构象研究和蔗糖酶相互作用。结果表明,这些药物与游离酶和酶底物复合物结合,并伴有高铬性。这表明,在药物与酶结合后,酶的色氨酸残基转移到疏水介质中。结论三氟拉嗪和氟哌啶醇对蔗糖酶均有非竞争性抑制作用。三氟拉嗪与该酶结合引起的动力学参数和构象变化与氟哌啶醇不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interaction of Antipsychotic Drugs with Sucrase, Kinetics and Structural Study.
BACKGROUND In patients with the Congenital Sucrase-Isomaltase Deficiency (CSID), who lack intestinal sucrase-isomaltase enzyme, a suspension of yeast sucrase is applied as a drug to compensate the enzyme deficiency. While antipsychotic drugs are used for the treatment of schizophrenia, administering multiple drugs at the same time may counteract each other. METHODS In this study, the interaction between trifluoperazine and haloperidol as antipsychotic drugs on oral drug yeast sucrase was investigated. In this regard, the kinetic parameters of enzyme were determined in the presence or absence of the drugs. The kinetic parameters of the drugs such as Ki and IC50 were also calculated. Lineweaver - Burk plot was used to reveal the type of inhibition. RESULTS The results showed that both drugs could reduce sucrase activity and decrease the Vmax of the enzyme by non-competitive inhibition. The IC50 and Ki values of the drugs were determined to be 0.7 and 0.068 mM and 0.45 and 0.063 mM for haloperidol and trifluoperazine, respectively. The results suggested that trifluoperazine binds to the enzyme with higher affinity than haloperidol. Fluorescence measurement was used for conformational investigations of the drugs and sucrase interaction. It was shown that the drugs bind to free enzyme and enzyme-substrate complex which are accompanied with hyperchromicity. This suggests that tryptophan residues of the enzyme transferred to hydrophobic medium after binding of the drugs to the enzyme. CONCLUSION The finding of this research revealed that both trifluoperazine and haloperidol could inhibit sucrase in non-competitive manner. The kinetic parameters and conformational changes due to binding of trifluoperazine to the enzyme were different from that of haloperidol.
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来源期刊
Current clinical pharmacology
Current clinical pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
3.60
自引率
0.00%
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0
期刊介绍: Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.
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