A new study brings us one step closer to a birth control pill for men, and it comes from an unlikely source: a plant-derived poison once used on the arrows of African warriors.

Yes, you read it right. Researchers suggest that a plant extract known as ouabain—a potentially toxic substance that can stop the heart — could serve as an oral contraceptive for men.

This is after finding that a modified form of the compound safely reduced sperm motility in male rats.

Study co-author Gunda Georg—who works in the Department of Medicinal Chemistry at the University of Minnesota's College of Pharmacy in Minneapolis—and her colleagues recently published their findings in the Journal of Medicinal Chemistry.

When it comes to oral contraception, women have a wealth of options. But for men, the choice is between condoms or a vasectomy. But researchers hope that this could soon change, with great strides being made toward the world's first oral contraceptive for men.

In 2016, a study from Georg and colleagues identified a number of compounds that could be modified to make them viable candidates for male birth control.

The latest study focuses on one compound in particular: ouabain.

Ouabain and male fertility

Ouabain, a substance that derives from the African plants Strophanthus gratus and Acokanthera schimperi, is a toxic compound that, in high doses, can cause cardiac arrest.

It was also traditionally used in African warfare; warriors used to coat the ends of their arrows with the substance in the hope that it would poison their enemies.

Today, ouabain is sometimes used in low doses for the treatment of certain heart conditions; it can help to control blood pressure and heart rate. That being said, because of the compound's toxicity, its use is not widespread.

Ouabain works by inhibiting proteins in cell membranes called Na,K-ATPases. These proteins are comprised of subunits, many of which are found in heart tissue.

However, the researchers note that one Na,K-ATPase subunit — known as Na,K-ATPase α4—is present in adult sperm cells, and research has shown that this subunit plays a significant role in male fertility.

Although previous studies have indicated that ouabain could reduce fertility in men, the compound as it stands would not be suitable as a male contraceptive; it would not only inhibit Na,K-ATPase α4 in sperm, but it would also block cardiac Na,K-ATPase subunits, which could cause severe heart damage.

With this in mind, Georg and team sought to modify ouabain so that it would target Na,K-ATPase α4, while steering clear of Na,K-ATPase subunits in the heart.

Compound reduced sperm motility in rats

The scientists tested a number of different ouabain modifications for the new study, and they found that by removing a sugar group and the lactone group from the compound and replacing the latter with a triazole group, they created a compound that could selectively target the Na,K-ATPase α4 subunit in sperm cells.

On testing this newly created form of ouabain in male rats, they found that it was able to bind to the Na,K-ATPase α4 subunit in sperm and reduce their motility, or ability to swim. Poor motility can hinder sperm's ability to travel through the female reproductive tract and fertilize an egg.

Importantly, the researchers found that their modified form ouabain produced no toxic effects in the rats.

Also, they point out that the effects of the compound on sperm motility should be reversible; since Na,K-ATPase α4 subunits are only present on mature sperm cells, any sperm cells produced after treatment with the ouabain-derived compound should not be affected.

Further studies are needed before any conclusions can be made about the use of ouabain as an oral contraceptive for men, but the researchers believe that their modified version could be a potential candidate.

The team concludes:

"This novel scaffold represents an attractive chemical structure for further development of a highly specific male contraceptive."