Mercurial diuretics act primarily on active transport of sodium. The mechanism of action probably involves a firm attachment of mercury to a sulfhydryl group of a renal enzyme that helps to generate energy for sodium transport, or to a sodium carrier. In either case, the transporting system fails. To date, no known enzyme or specific carrier substance has been identified as the receptor for mercurials.
Structure-activity analysis makes it necessary to reject the diuretic structure proposed by Kessler et at. (95), for there are too many exceptions to it (185). Although there is no remaining barrier to acceptance of mercuric ion as the most active form of mercury, the intact molecule hypothesis should not be discarded because there is still reason to believe that a single attachment to a receptor through one valence of mercury may also produce a diuresis.
A better understanding of mechanism of action depends on the acquisition of additional information on: (a) the carrier system that transports sodium; (b) the mechanism whereby acidosis potentiates the diuretic action of mercuric cysteine; (c) renal transport and distribution of mercurials, especially diuretic compounds that do not pile up in large amounts (e.g., mersalyl); (d) the identity of the specific renal receptor to which mercurials bind.
- 1968 by The Williams & Wilkins Co.