Diuretics organic mercurials

Other organic mercurials similar in chemical stmcture to chlormerodrin are meraHuride/7(94-2(9-j5y, mercaptomerin/2 (922J-< 4-/7, and mersalyl [486-67-9]. Mercury-based diuretics (qv) are no longer in use. 

Organic mercurial diuretics also inhibit salt transport in the TAL but are no longer used because of their toxicity. 

In the 1920s, researchers discovered the diuretic effects of substances known as organic mercurials that were used to treat a heart disorder related to syphilis. They... 

The phenoxyacetic acid structure had been found to be a good carrying moiety in organic mercury diuretics. 

Compounds with high diuretic potency resulted from the observation in 1919 that an antisyphilitic organic mercury compound, merbaphen, also had strong diuretic properties. It was demonstrated the next year that the drug increased the excretion rate of Na+ and Cl" (i.e., it was saluretic). 

Organic mercurial diuretics were widely employed prior to the introduction of thiazides and a host of other potent non-mereurial diuretics, but now have been virtually superseded by these orally aetive drugs that are found to be both potent and less toxic. 

It was soon learned that the sulfonamide portion of an active diuretic molecule could not be monosubstituted or disubstituted. It was reasoned that a more acidic sulfonamide would bind more tightly to the carbonic anhydrase enzyme. Synthesis of more acidic sulfonamides produced compounds more than 2,500-fold more active than sulfanilamide. Acetazolamide was Introduced In 1953 as an orally effective diuretic drug. Before that time, the organic mercurials, which commonly required Intramuscular Injection, were the principal diuretics available. 

The diuretic activity and pharmacological properties of the organic mercurials and of ethacrynic acid and furosemide are already well-documented. Discussion of these agents will be confined to recent studies pertaining to their biochemical mechanisms of action. 

The present classes of diuretic drugs have contributed much useful information to the chemist and to the biologist. From the mercurial diuretics, on the biological side, some facts have been learned about their site of action, if not the exact mechanism of action, and they have been helpful in the study of the site of the transport of various ions by the kidney. The importance of sulfhydryl enzyme systems has been demonstrated, although the specific enzyme has not been identified. On the chemical side, the chemist has learned about the structural requirements for useful activity, the nature of the carbon-mercury attachment, and the organic structures most useful as carrying moieties for mercury. 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

For a great many years, mercurial compounds were the most powerful of all known diuretics, but the introduction of chlorthiazide in 1958, followed by other types of purely organic diuretics, made the mercurial diuretics seem toxic and inefficient by comparison and they are no longer used. Mercurial diuresis depended on the liberation of mercuric ions by the acidity of the kidney fluids and the blockade by these ions of a key mercapto-group in the kidney enzyme responsible for resorption of sodium chloride. 

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