Researchers are developing a male birth control pill based on ouabain, a plant extract that African warriors and hunters traditionally used as a heart-stopping poison on their arrows.
Two types of African plants make ouabain, but mammals also produce it in their bodies, though at lower levels that are thought to help control blood pressure. In fact, doctors sometimes prescribe small doses to treat heart attack patients.
Ouabain disrupts the passage of sodium and calcium ions through Na,K-ATPases, which are made up of protein subunits and are found in cell membranes. Some subunits are found in cardiac tissue, but one type of subunit called α4 is found only in sperm cells. This protein is known to be critical in fertility — at least in male mice. Ouabain binds strongly to α4, 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 Professor Gunda Georg, working with her University of Kansas collaborator Gustavo Blanco and other colleagues, set out to design ouabain analogs that are far more likely to bind to the α4 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 α4 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 showed no toxicity in a study with rats. The researchers say that the contraceptive effect should be reversible because α4 is only found on mature sperm cells. That means sperm cells produced after stopping treatment with the ouabain derivative shouldn’t be affected.
The authors received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Their findings were published in ACS’ Journal of Medicinal Chemistry.
Prospective Birth Control Pill for Men Has its Origin in an Arrow Poison was originally published on the University of Minnesota website.