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三环类抗抑郁药物电荷转移复合物形成及过氧化物酶抑制作用的光谱分析:潜在的抗甲状腺作用

Spectroscopic analysis of charge transfer complex formation and peroxidase inhibition with tricyclic antidepressant drugs: potential anti-thyroid action.

作者信息

Rousseau A, Comby F, Buxeraud J, Raby C

机构信息

Department of Biophysics-Informatique, Faculty of Pharmacy, University of Limoges, France.

出版信息

Biol Pharm Bull. 1996 May;19(5):726-8. doi: 10.1248/bpb.19.726.

Abstract

Inspection of the chemical structures of tricyclic antidepressant drugs indicates that they might interfere with the synthesis of thyroid hormones. This iatrogenic potential was demonstrated in vitro by the spectrophotometric detection in both the visible and UV regions of the formation of a complex between antidepressants and iodine. The values of Kc, the formation constant of the drug-iodine complex, were calculated. The concentration of antidepressant which led to a 50% inhibition (IC50) of horseradish peroxidase was also determined. The anti-thyroid activity of drugs can be evaluated from these two parameters, Kc and IC50. The results were compared to those obtained with methimazole, a reference anti-thyroid agent. Antidepressants derived from imipramine appeared to have anti-thyroid activity. This result is now awaiting confirmation in animal experiments.

摘要

对三环类抗抑郁药化学结构的检查表明,它们可能会干扰甲状腺激素的合成。通过分光光度法在可见光和紫外区域检测抗抑郁药与碘形成的复合物,在体外证明了这种医源性潜力。计算了药物 - 碘复合物的形成常数Kc的值。还测定了导致辣根过氧化物酶50%抑制率(IC50)的抗抑郁药浓度。可以从这两个参数Kc和IC50评估药物的抗甲状腺活性。将结果与用作为参考抗甲状腺剂的甲巯咪唑所获得的结果进行比较。源自丙咪嗪的抗抑郁药似乎具有抗甲状腺活性。这一结果目前正在等待动物实验的证实。

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