Transport and excretion of uric acid in man. III. Physiologic significance of the uricosuric effect of caronamide

Wolfson, William Q.; Cohn, Clarence; Levine, Robert J.; Huddlestun, B.

doi:10.1016/s0002-9343(48)90402-1

Cited by 26 publications

(7 citation statements)

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“…Probenecid and carinamide are similar in their chemical structure and uricosuric effects [13,81]. However, probenecid has higher potency and effectiveness with regard Cardiovasc Toxicol (2012) 12:1- 9 3 to its effects on the proximal renal tubule and therefore can be given in lower doses and with stronger effects [12,32].…”

Section: Probenecid and Goutmentioning

confidence: 99%

The History and Future of Probenecid

et al. 2011

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Probenecid was initially developed with the goal of reducing the renal excretion of antibiotics, specifically penicillin. It is still used for its uricosuric properties in the treatment in gout, but its clinical relevance has sharply fallen and is rarely used today for either. Interestingly, throughout the last 60 years, there have been a host of apparently unrelated studies using probenecid in the clinical and basic research arena, including its potential use in the diagnosis and treatment of depression and its use to prevent fura-2 leakage in calcium transient studies. Recently, it has been shown that it is also an agonist of the Transient Receptor Potential Vanilloid 2 channel. Due to its unique action and new findings implicating TRPV channels in physiology and in disease, probenecid may have a new future as a research tool, and perhaps as a clinical agent in the neurology and cardiology fields. We review the history of probenecid in this paper and its potential future uses.

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Section: Probenecid and Goutmentioning

confidence: 99%

The History and Future of Probenecid

et al. 2011

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“…Ample experimental evidence attests to the fact that urate is virtually not bound by serum proteins in man or experimental animals (3)(4)(5)(6) I t is appropriate to begin with the alkylsulfonamidobenzoic acid, carinamide, formerly referred to as caronamide (Figure l), synthesized in 1946 by Sprague and Ziegler (8) originally to enhance the blood levels of penicillin. Subsequently its very modest uricosuric activity was fortuitously discovered in man by Wolfson et a1 (9) in 1948. I t soon became evident that because of the very high daily oral dosage required (8 to 12 g), by today's standards an astronomical amount, and because of the appearance of significant side effects, a newer more potent agent had to be developed in which the effective daily dose could (10) were the first to demonstrate simultaneous tubular secretion and tubular reabsorption of carinamide, or of any other drug for that matter.…”

Section: George M Fanelli Jrmentioning

confidence: 97%

Uricosuric agents

Fanelli

1975

Arthritis & Rheumatism

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By definition a uricosuric agent is one that facilitates the renal excretion of uric acid presumably by specific inhibition of its tubular reabsorption and secretion. Even though in most instances (with possible exceptions to be discussed shortly) both transport systems are inhibited to some degree, the predominant pharmacologic effect is on urate reabsorption at the luminal membrane with the net effect being uricosuria. An excellent review on uricosuric drugs has been published by the late Dr. Alexander B. Gutman Basic to the understanding of the mechanism of action of uricosuric agents and renal urate transport in general are the following postulates formulated by Weiner and Fanelli (2): a) Most of urate reabsorption occurs in the proximal tubule. b) Uricosuric agents act by depressing proximal reabsorption of urate. c) Drugs that depress urate reabsorption do so from the luminal aspect of the tubule. d) Uric acid is secreted in the proximal tubule. e) T h e secretory flux for urate (and consequently the reabsorptive flux) is large. f) A variety of compounds, uricosuric or not, inhibit the secretory flux. g) T h e urate secretory mechanism is probably different from the p-amino-(1).

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“…We had to wait until 1950 for the development of a modified caronamide (27), which became available as probenecid (Benemid), an effective uricosuric agent. Gutman and Yu (28) was immediately accepted for presentation.…”

Section: +mentioning

confidence: 99%

Clinical experiences

Talbott

1975

Arthritis & Rheumatism

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Transport and excretion of uric acid in man. III. Physiologic significance of the uricosuric effect of caronamide

Cited by 26 publications

References 0 publications

The History and Future of Probenecid

The History and Future of Probenecid

Uricosuric agents

Clinical experiences

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