Ouabain is a glycoside for the heart and, in lesser doses, it can be utilized to treat hypotension as well as some arrhythmias.
It works by blocking the Na/K-ATPase, which is also known as the sodium-potassium-ion pump.
However, modifications to the alpha-subunit Na+/K+-ATPase, through amino acid substitutions were observed on specific species. Specifically the herbivore-insect species which have led to resistance to toxins.
This substance has been classified a highly dangerous chemical throughout 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 stringent reporting requirements by all facilities that manufacture, store, or utilize it in large quantities.
ouabain
Sources
Ouabain is located in the roots stems, leaves, as well as the seeds of Acokanthera Schimperi and Strophanthus Gracious plants Both are indigenous to the eastern part of Africa.
Mechanism of action
Ouabain is a glycoside in the heart which acts by inhibiting sodium-potassium ion-pump (but it’s not selective). Once the ouabain has bound to this enzyme, it ceases functioning, leading to an increase in intracellular sodium.
This rise in intracellular sodium diminishes the function. That the sodium calcium exchanger (NCX) that pump one calcium ion out the cell, and three sodium ions into cells down the gradient of their concentration.
This is why the decrease in the gradient of concentration of sodium in the cell. Which happens when the Na/K-ATPase enzyme is blocked hinders the capability to allow the NCX to perform its function.
This causes an increase in intracellular calcium. This leads to increased cardiac contractility as well as an increase in the cardiac vagal tone. The changes in ionic gradients that are caused by ouabain may alter the voltage of the membranes of cells, resulting in arrhythmias of the heart.
The signs
A high dose of ouabain may be identified by the appearance of these symptoms. That include rapid twitching in the chest and neck muscles breathing distress, an increase and irregular heartbeat, increase in blood pressureand convulsions wheezing and clicking, as well as gasping rattle.
The cause of death is cardiac arrest.
Toxicology
Ouabain is a very toxic chemical with an LD50 that is 5 mg/kg it is administered in rodents’ stomachs.
But, it is not bioavailable and is not well absorbed by the digestive tract. As most of the oral dose is eliminated. Injecting it intravenously results in higher available levels and has been demonstrated to reduce levels of LD50 by 2.2 mg/kg, even in rodents.
After intravenous administration the beginning of the action takes place within 2 to 10 minutes. In humans with the greatest effect lasting over 1.5 hours.
Ouabain is eliminated via excretion from the kidney, which is mostly unaltered.
Ouabain is eliminated via excretion from the kidney, which is mostly unaltered.
The biological impacts
Endogenous ouabain
In the year 1991, a sodium pump inhibitor with high affinity. Which was not different from ouabain was found in the circulation of humans and suggested. One possible mediators of the long-term blood pressure. As well as the higher salt excretion in response to the loading of salt and volume.
This substance was a blocker of sodium pump, which was similar to digitalis. Many different analytical methods resulted in the conclusion. That the circulating chemical was called ouabain. That humans produced the hormone as an exogenous one.
The majority scientists believed that the inhibitor was endogenous ouabain, and the evidence was convincing to support the idea its production within the adrenal gland.
A first speculation about the data from an analytical perspective resulted in the hypothesis that the endogenous ouabain could be the 11 epimer i.e. It was an isomer of the plant ouabain.
But, this possibility was ruled out by a variety of methods such as the synthesizing of 11 epimers as well as the evidence that it exhibits distinct chromatographic characteristics in comparison to ouabain.
The most important thing is that the first observations about the discovery orabain as a mammal was replicated and verified using a variety tissue samples from three distinct continents using advanced analytical techniques which are described elsewhere.
Medical applications
While ouabain is not allowed in the USA and Canada, it is still used it is still used in France and Germany intravenous orabin is a well-established treatment for treatments for heart failure and some are still advocating its use either intravenously or orally for angina pectoris and myocardial infarction, despite its weak and varied absorption.
The benefits of ouabain with respect to the prophylaxis as well as treatment. These diseases have been proven by numerous studies.
Animal usage of ouabain
The African crested rodent (Lophiomys imhausi) has a wide hair strip with a white border covering a large area of hairy skin that runs along the side.
When the animal is scared or is excited, the mane on its back raises, and the flank strip splits open, showing the glandular part. Hairs on the flanks are specific; at their edges they look like normal hairs, but they are soft, flexible, and absorptive.
Rats are notorious for chewing on the bark and roots of the Poison-arrow plant (Acokanthera schimperi), which has ouabain.
After chewing the tree instead of swallowing it. It spreads the mucus onto its special flank hairs, which are specially adapted for absorption of the mix. The result is a defense mechanism that could sicken the predators that try to take it in.
Synthesis
The complete synthesizing of ouabain was accomplished in 2008 by the Deslongchamps lab in Canada. The synthesis was carried out in the hope that polyanionic ciclization (double Michael addition followed by aldol condensation) could lead to a tetracyclic intermediate that has the expected performance.
The figure below illustrates the most important steps involved in the synthesis of ouabain.
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