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新型利尿药奥唑啉酮光学活性异构体的研究。II. d-奥唑啉酮对速尿诱导利尿作用的抑制。

Studies with the optically active isomers of the new diuretic drug ozolinone. II. Inhibition by d-ozolinone of furosemide-induced diuresis.

作者信息

Greven J, Beckers M, Defrain W, Meywald K, Heidenreich O

出版信息

Pflugers Arch. 1980 Mar;384(1):61-4. doi: 10.1007/BF00589515.

DOI:10.1007/BF00589515
PMID:7189867
Abstract

The effect of the non-diuretic dextrorotatory isomer of ozolinone on furosemide-induced diuresis was studied by means of clearance and micropuncture techniques in rats. After intravenous injection, d-ozolinone antagonized the furosemide-induced increase in renal fluid and electrolyte excretion in a dose-related manner. Microperfusion experiments of Henle's loop in vivo revealed that d-ozolinone did not interfere with the action of furosemide at this tubular site. However, d-ozolinone markedly decreased the furosemide to inulin clearance ratio, presumably as a consequence of inhibition of furosemide secretion into the proximal tubules. It is assumed that, in consequence of a high affinity for the proximal organic acid transport system, d-ozolinone depresses proximal tubular furosemide secretion and prevents transfer of this diuretic to the tubular fluid. Thus, under the influence of d-ozolinone, furosemide cannot reach the loop of Henle in sufficient amounts and its diuretic effect is blocked.

摘要

采用清除率和微穿刺技术,在大鼠身上研究了奥佐利酮的非利尿右旋异构体对呋塞米诱导利尿作用的影响。静脉注射后,d-奥佐利酮以剂量相关的方式拮抗呋塞米诱导的肾液体和电解质排泄增加。体内对亨氏袢进行微灌注实验表明,d-奥佐利酮在此肾小管部位不干扰呋塞米的作用。然而,d-奥佐利酮显著降低了呋塞米与菊粉的清除率比值,推测这是由于抑制了呋塞米向近端小管的分泌。据推测,由于对近端有机酸转运系统具有高亲和力,d-奥佐利酮会抑制近端小管呋塞米的分泌,并阻止这种利尿剂转移到肾小管液中。因此,在d-奥佐利酮的影响下,呋塞米无法足量到达亨氏袢,其利尿作用被阻断。

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引用本文的文献

1
Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function.依他唑啉/奥唑啉酮在肾功能正常和受损的高血压患者中的药效学和药代动力学。
Eur J Clin Pharmacol. 1984;26(6):687-93. doi: 10.1007/BF00541926.
2
Molecular actions of diuretics.利尿剂的分子作用
Klin Wochenschr. 1982 Oct 1;60(19):1258-63. doi: 10.1007/BF01716734.
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Diuretics. Clinical pharmacology and therapeutic use (Part I).利尿剂。临床药理学与治疗应用(第一部分)

本文引用的文献

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2
[A simple colorimetric method of inulin determination in renal clearance studies on metabolically normal subjects and diabetics].[一种用于代谢正常受试者和糖尿病患者肾脏清除率研究中菊粉测定的简单比色法]
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Studies with the optically active isomers of the new diuretic drug ozolinone. I. Differences in stereoselectivity of the renal target structures of ozolinone.新型利尿药奥唑啉酮光学活性异构体的研究。I. 奥唑啉酮肾脏靶结构的立体选择性差异。
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Pflugers Arch. 1980 Mar;384(1):57-60. doi: 10.1007/BF00589514.
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Influence of probenecid and alterations in acid-base balance of the saluretic activity of furosemide.丙磺舒及酸碱平衡改变对呋塞米利尿活性的影响。
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[Renal excretion of the new diuretic Furosemide].新型利尿剂速尿的肾脏排泄
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6
A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.布美他尼与呋塞米在犬体内的利尿及组织分布比较研究。
J Pharmacol Exp Ther. 1976 Jun;197(3):697-702.