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Potential male birth control pill developed from arrow poison

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By Oluwaseyi Adeshina

Women have many options for oral contraceptives that are safe, effective and reversible, but despite decades of research, men have none.

Now, scientists report a rat study in ACS’ Journal of Medicinal Chemistry that shows they finally have a good lead for a male birth control pill. It’s based on ouabain, a plant extract that African warriors and hunters traditionally used as a heart-stopping poison on their arrows.

New male birth control pill set to debut

Two types of African plants make ouabain. Mammals also produce it in their bodies, though at lower levels that are thought to help control blood pressure; doctors sometimes prescribe small doses of the compound to treat heart attack patients. Ouabain disrupts the passage of sodium and calcium ions through the membrane protein Na,K-ATPases, which are are found in cell membranes and are made up of protein subunits.

Some subunits are found in cardiac tissue, but one type of subunit called ?4 is found only in sperm cells. This protein is known to be critical in fertility — at least in male mice. Ouabain binds strongly to ?4, but it also binds to other Na,K-ATPase subunits, albeit less tightly.

Prior clinical studies have shown that ouabain curbs fertility in men. However, ouabain itself isn’t an option as a contraceptive because of the risk of heart damage. So Gunda Georg, Gustavo Blanco and colleagues set out to design ouabain analogs that are far more likely to bind to the ?4 protein in sperm than to subunits found in heart tissue.

By removing a sugar group from ouabain and also replacing its lactone group with a triazole group, the researchers created a derivative that is particularly good at zeroing in on ?4 in sperm cells in rats. Once bound, it interferes with the cells’ ability to swim, which is essential to its role in fertilizing an egg, the scientists showed. The compound had no toxicity in rats.

The researchers say that the contraceptive effect should be reversible because ?4 is only found on mature sperm cells. That means sperm cells produced after stopping treatment with the ouabain derivative shouldn’t be affected.

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