Ouabain or (from Somali waabaayo, "arrow poison" through French ouabaïo) also known as g-strophanthin, is a plant derived toxic substance that was traditionally used as an arrow poison in eastern Africa for both hunting and warfare. Ouabain is a cardiac glycoside and in lower doses, can be used medically to treat hypotension and some arrhythmias. It acts by inhibiting the Na/K-ATPase, also known as the sodium-potassium ion pump. However, adaptations to the alpha-subunit of the Na+/K+-ATPase via amino acid substitutions, have been observed in certain species, namely some herbivore- insect species, that have resulted in toxin resistance. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities. Sources Ouabain can be found in the roots, stems, leaves, and seeds of the Acokanthera schimperi and Strophanthus gratus plants, both of which are native to eastern Africa. Mechanism of action Ouabain is a cardiac glycoside that acts by inhibiting the Na+/K+–ATPase sodium-potassium ion pump (but it is not selective). Once ouabain binds to this enzyme, the enzyme ceases to function, leading to an increase of intracellular sodium. This increase in intracellular sodium reduces the activity of the sodium-calcium exchanger (NCX), which pumps one calcium ion out of the cell and three sodium ions into the cell down their concentration gradient. Therefore, the decrease in the concentration gradient of sodium into the cell which occurs when the Na/K-ATPase is inhibited reduces the ability of the NCX to function. This in turn elevates intracellular calcium. This results in higher cardiac contractility and an increase in cardiac vagal tone. The change in ionic gradients caused by ouabain can also affect the membrane voltage of the cell and result in cardiac arrhythmias. Symptoms An overdose of ouabain can be detected by the presence of the following symptoms: rapid twitching of the neck and chest musculature, respiratory distress, increased and irregular heartbeat, rise in blood pressure, convulsions, wheezing, clicking, and gasping rattling. Death is caused by cardiac arrest. Toxicology Ouabain is a highly toxic compound with a LD50 of 5 mg/kg when administered orally to rodents. However, ouabain has a low bioavailability and is absorbed poorly from the alimentary tract as so much of the oral dose is destroyed. Intravenous