Ouabain

  Ouabain ('wa:ben, wa:'bein) is the familiar name of g-strophanthin, a poisonous cardiac glycoside.

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Sources

Ouabain (g-strophanthin) is found in the ripe seeds of African plants Strophanthus gratus and Acokanthera ouabaio. k-strophanthin is found in the ripe seeds of Strophanthus kombé.

Function

Ouabain blocks the Na⁺/K⁺-ATPase in higher concentrations which are attainable in vitro or with intravenous dosage. This is the original use of ouabain; digoxin is a generally more popular compound used for similar indications (atrial fibrillation and congestive heart failure).

A recent concept is that at low concentrations ouabain in fact has the opposite effect, namely stimulation of the Na-K-ATPase.^[1] This property is not exhibited by digoxin.^[2]

Endogenous ouabain and ouabain mimics

In 1991 ouabain was identified as an endogenous hormone.^[3] After some controversial results it is now probable that endogenous ouabain is an isomer of plant ouabain.^[4] Ouabain is synthesized in the adrenal gland^[5] and in the hypothalamus^[6]. It is also produced in the heart, augmentedly in the condition of oxygen deficiency.^[7]

Its exact mode of action and physiological significance is not yet determined. In normal human plasma, circulating levels ranging from 3 - 190 picoMol ouabain have been found, with higher levels in congestive heart failure, essential hypertension and some cancers. It has been suggested that these low concentrations of ouabain may stimulate the Na+/K+-ATPase while the higher levels achieved during intravenous therapy or in pathophysiological disorders may inhibit the NaK-pump.^[1]

In the years following the discovery of ouabain in the human circulation, it was found in the adrenal glands of cows^[8] and dogs.^[9]

Uses

Ouabain is used worldwide extensively by scientists for in-vitro-studies to block the sodium pump (Na-K-ATPase). In many non rodent species, low concentrations of this substance (i.e., in the nanomolar range) provide effective stimulation of the NaK-pump. The issue in rodents is more complicated because there are different isoforms of the NaK-pump - some of which are very sensitive to ouabain while others are not. Ouabain is no longer widely used for the treatment of human heart failure. However, in France and Germany, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use by mouth in angina pectoris and myocardial infarction. There is limited anecdotal evidence for improved efficacy of ouabain relative to digoxin in a small number of patients. However, no well controlled research exists that proves or disproves the efficacy this practice.

References