administration results in greater available concentrations and has been shown to decrease the LD50 to 2.2 mg/kg, also in rodents. After intravenous administration, the onset of action occurs within 2–10 minutes in humans with the maximum effect enduring for 1.5 hours. Ouabain is eliminated by renal excretion, largely unchanged. Biological effects Endogenous ouabain In 1991, a specific high affinity sodium pump inhibitor indistinguishable from ouabain was first discovered in the human circulation and proposed as one of the potential mediators of long term blood pressure and the enhanced salt excretion following salt and volume loading. This agent was an inhibitor of the sodium pump that acted similarly to digitalis. A number of analytical techniques led to the conclusion that this circulating molecule was ouabain and that humans were producing it as an endogenous hormone. A large portion of the scientific community agreed that this inhibitor was endogenous ouabain and that there was strong evidence to indicate that it was synthesized in the adrenal gland. One early speculative interpretation of the analytical data led to the proposal that endogenous ouabain may have been the 11 epimer, i.e., an isomer of plant ouabain. However, this possibility was excluded by various methods including the synthesis of the 11 epimer and the demonstration that it has different chromatographic behavior from ouabain. Critically, the primary observations concerning the identification of ouabain in mammals were repeated and confirmed using a variety of tissue sources on three different continents with advanced analytical methods as summarized elsewhere Despite widespread analytical confirmation, some questioned whether or not this endogenous substance is ouabain. The arguments were based less upon rigorous analytical data but more on the fact that immunoassays are neither entirely specific nor reliable. Hence, it was suggested that some assays for endogenous ouabain detected other compounds or failed to detect ouabain at all. Additionally, it was suggested that rhamnose, the L-sugar component of ouabain, could not be synthesized within the body despite published data to the contrary. Yet another argument against the existence of endogenous ouabain was the lack of effect of rostafuroxin (a first generation ouabain receptor antagonist) on blood pressure in an unselected population of hypertensive patients. Medical uses Ouabain is no longer approved for use in the USA. In France and Germany, however, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use intravenously and orally